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Healthcare breakthroughs are extending the lives of multiple sclerosis (MS) patients and cancer survivors, creating a growing cohort of individuals navigating a dual diagnosis. Determining the relationship between MS and cancer risk remains challenging, with inconclusive findings confounded by age, risk exposures, comorbidities, genetics and the ongoing introduction of new MS disease-modifying therapies (DMTs) across study periods. This research places significant emphasis on cancer survival, with less attention given to the impact on MS outcomes. Our review explores the existing literature on MS, cancer risk and the intersection of DMTs and cancer treatments. We aim to navigate the complexities of managing MS in cancer survivors to optimise outcomes for both conditions. Continuous research and the formulation of treatment guidelines are essential for guiding future care. Collaboration between neuro-immunology and oncology is crucial, with a need to establish databases for retrospective and ultimately prospective analysis of outcomes in these rapidly evolving fields. [ABSTRACT FROM AUTHOR]

Fascinatingly, an abundance of recent studies has subscribed to the importance of cytotoxic immune mechanisms that appear to increase the risk/trigger for many progressive neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with the neuroinflammatory cascades, such as ageing, immunologic dysfunction, and eventually disruption of the blood–brain barrier and the "cytokine storm", appear to be orchestrated mainly through the activation of microglial cells and communication with the neurons. The inflammatory processes prompt cellular protein dyshomeostasis. Parkinson's and Alzheimer's disease share a common feature marked by characteristic pathological hallmarks of abnormal neuronal protein accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or in the case of AD, they are Aβ deposits and tau-containing neurofibrillary tangles. Subsequently, these abnormal protein aggregates further elicit neurotoxic processes and events which contribute to the onset of neurodegeneration and to its progression including aggravation of neuroinflammation. However, there is a caveat for exclusively linking neuroinflammation with neurodegeneration, since it's highly unlikely that immune dysregulation is the only factor that contributes to the manifestation of many of these neurodegenerative disorders. It is unquestionably a complex interaction with other factors such as genetics, age, and environment. This endorses the "multiple hit hypothesis". Consequently, if the host has a genetic susceptibility coupled to an age-related weakened immune system, this makes them more susceptible to the virus/bacteria-related infection. This may trigger the onset of chronic cytotoxic neuroinflammatory processes leading to protein dyshomeostasis and accumulation, and finally, these events lead to neuronal destruction. Here, we differentiate "neuroinflammation" and "inflammation" with regard to the involvement of the blood–brain barrier, which seems to be intact in the case of neuroinflammation but defect in the case of inflammation. There is a neuroinflammation-inflammation continuum with regard to virus-induced brain affection. Therefore, we propose a staging of this process, which might be further developed by adding blood- and CSF parameters, their stage-dependent composition and stage-dependent severeness grade. If so, this might be suitable to optimise therapeutic strategies to fight brain neuroinflammation in its beginning and avoid inflammation at all. [ABSTRACT FROM AUTHOR]

Background: The herbal Poria cocos -Liquorice drug pair (PLDP) possesses the ability to be a diuretic, stimulating the spleen and benefiting the kidney, which plays an important role in the treatment of Henoch–Schönlein purpura nephritis (HSPN). However, the mechanism of action is unknown. Objectives: Through the method of network pharmacology, this research sought to determine the mechanism of PLDP against HSPN. Materials and Methods: The screening of active ingredients in PLDP was conducted by Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases, while their targets were obtained from the TCMSP and Swiss Target Prediction (STP) databases. The genes of HSPN were searched by OMIM, DisGeNET, and GeneCards databases. Then, the common targets of active ingredients in PLDP and HSPN were mapped by Venn analysis. To get the main targets, the researchers utilized the STRING database to construct the protein–protein interaction (PPI) network of the common targets. Then, the function of gene ontology (GO) and the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the main targets were examined on the Metascape database to identify the molecular mechanism of PLDP against HSPN. The most relevant signaling pathways with HSPN screened from the top 20 pathways were defined as the key pathways. Finally, the "active ingredient-main target-key pathway" network was built in order to identify the core targets and key active ingredients of PLDP against HSPN. Results: There were 101 active ingredients and 360 targets for PLDP. One hundred and fifty-seven genes for HSPN and 35 common targets between PLDP and HSPN were identified. Through the "active ingredient-main target-key pathway" network, quercetin, kaempferol, polyporenic acid C, dehydrotumulosic acid, poricoic acid A, and naringenin were identified as key active ingredients; TNF, NOS3, RELA, AKT1, ICAM1, and IFNG were identified as core targets; and the key pathways include TNF signaling pathways, HIF-1 signaling pathways, and IL-17 signaling pathways. Conclusion: The research initially investigated the pathways, active ingredients, and targets involved in PLDP against HSPN. The mechanism appears to be linked to its immunomodulatory and anti-inflammatory properties, thus establishing a scientific foundation for further investigation. [ABSTRACT FROM AUTHOR]

The present study tested the symbiotic effects of dietary multi-strain Bacillus probiotics (MSB) (Bacillus licheniformis, B. pumilus, and B. subtilis) in Nile tilapia (Oreochromis niloticus) exposed to Aspergillus flavus infection. Furthermore, this study investigated water quality, growth performance, blood metabolites, histological morphology, immune regulatory genes, and resistance to A. flavus infection. For 70 days, fish (n = 240) were divided into four groups in triplicate: T0 (control group; MSB0), T1 (1 g/kg, MSB1), T2 (2 g/kg, MSB2), and T3 (3 g/kg, MSB3). The immune response was then assessed by challenging all fish groups with the A. flavus pathogen. The results showed that the rearing water quality, fish growth, and blood parameters, as well as total proteins, albumin, globulins, and amylase activity were significantly (P < 0.05) increased in all MSB-treated groups with the best results in MSB2 and MSB3 groups. Meanwhile, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and glucose levels were significantly (P < 0.05) modulated, particularly at higher concentrations of the probiotic mixture (MSB3 group). Fish fed with various levels of MSB showed a maintained histological structure of the hepatopancreas, intestine, and spleen tissues. The mRNA expression of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor receptor-1 (IGF-1R), and interleukin-8 (IL-8) were increased in a dose-dependent manner due to MSB dietary inclusion (P < 0.05). Conversely, the mRNA expression of interleukin-1β (IL-1β) gene was significantly decreased in MSB groups compared to untreated group (P < 0.05). Surprisingly, supplemented groups in Bacillus spp. probiotics exhibited significant modulations in all computed parameters. MSB supplementation improved the pathogenic tolerance of tilapia after change with A. flavus. The integration of growth performance, biochemical, and transcriptomic results confirms that the dietary intervention of multi-strain Bacillus spp. is symbiotic and enhances the benefits for the maintenance of O. niloticus' health, growth, and digestion. This is achieved by supporting growth genes, reducing inflammatory genes, and enhancing immune-antioxidant resistance to combat A. flavus infection. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is increasingly being used in medicine to enhance the speed and accuracy of disease diagnosis and treatment. AI-based image analysis is expected to play a crucial role in future healthcare facilities and laboratories, offering improved precision and cost-effectiveness. As technology advances, the requirement for specialized software knowledge to utilize AI applications is diminishing. Our study will examine the advantages and challenges of employing AI-based image analysis in the field of immunology and will investigate whether physicians without software expertise can use MS Azure Portal for ANA IIF test classification and image analysis. This is the first study to perform Hep-2 image analysis using MS Azure Portal. We will also assess the potential for AI applications to aid physicians in interpreting ANA IIF results in immunology laboratories. The study was designed in four stages by two specialists. Stage 1: creation of an image library, Stage 2: finding an artificial intelligence application, Stage 3: uploading images and training artificial intelligence, Stage 4: performance analysis of the artificial intelligence application. In the first training, the average pattern identification accuracy for 72 testing images was 81.94%. After the second training, this accuracy increased to 87.5%. Patterns Precision improved from 71.42 to 79.96% after the second training. As a result, the number of correctly identified patterns and their accuracy increased with the second training process. Artificial intelligence-based image analysis shows promising potential. This technology is expected to become essential in healthcare facility laboratories, offering higher accuracy rates and lower costs. [ABSTRACT FROM AUTHOR]

Recently, immunotherapies for antitumoral response have adopted conditionally activated molecules with the objective of reducing systemic toxicity. Amongst these are conditionally activated antibodies, such as PROBODY® activatable therapeutics (Pb-Tx), engineered to be proteolytically activated by proteases found locally in the tumor microenvironment (TME). These PROBODY® therapeutics molecules have shown potential as PD-L1 checkpoint inhibitors in several cancer types, including both effectiveness and locality of action of the molecule as shown by several clinical trials and imaging studies. Here, we perform an exploratory study using our recently published quantitative systems pharmacology model, previously validated for triple-negative breast cancer (TNBC), to computationally predict the effectiveness and targeting specificity of a PROBODY® therapeutics drug compared to the non-modified antibody. We begin with the analysis of anti-PD-L1 immunotherapy in non-small cell lung cancer (NSCLC). As a first contribution, we have improved previous virtual patient selection methods using the omics data provided by the iAtlas database portal compared to methods previously published in literature. Furthermore, our results suggest that masking an antibody maintains its efficacy while improving the localization of active therapeutic in the TME. Additionally, we generalize the model by evaluating the dependence of the response to the tumor mutational burden, independently of cancer type, as well as to other key biomarkers, such as CD8/Treg Tcell and M1/M2 macrophage ratio. While our results are obtained from simulations on NSCLC, our findings are generalizable to other cancer types and suggest that an effective and highly selective conditionally activated PROBODY® therapeutics molecule is a feasible option. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma is the most frequent and aggressive brain cancer. It is a highly immunology-driven disease as up to a third of its mass is composed of immune cells. Apart from immunology, imaging is a major research frontier. The VASARI (Visually AcceSAble Rembrandt Images) MRI feature set is a system designed to enable consistent description of gliomas using a set of defined visual features and controlled vocabulary. Even though imaging and immunology are both indispensable for glioblastoma phenotyping, a comprehensive integration of these two disciplines has not been performed so far. Material and methods: 76 patients from a previous glioblastoma immunotherapy clinical trial were retrospectively screened for the availability of peripheral blood immunology and tumor imaging data at baseline, i.e. at the start of the study. For 41 patients both were available. MRI were then analyzed via volumetry and VASARI morphometry. The resulting 27 imaging variables were linked with 67 peripheral blood immunology variables from flow cytometry and PCR and all potential relations were mapped. Results: In an initial broad screening, 94 imaging-immunology associations were discovered. Notably, features of the contrast-enhancing margin like its thickness and its shape were positively correlated with various T cell species including activated cytotoxic CD8+ T cells and central memory CD8+ T cells. The T2-volume was correlated with CD56+CD16− natural killer cells, and the necrosis volume was correlated with immunopolarizing mRNAs in the blood (IFN-γ, GATA3, ROR-gt). After multiple testing correction, two imaging-immunology associations were confirmed as significant: a thick contrast-enhancing margin was correlated with lower regulatory T cell markers in the blood and invasion of deep white matter was correlated with less T helper 17 factors. Conclusion: We here provide first evidence that imaging and peripheral blood immunology features can go hand in hand and that imaging variables can correlate with systemic immunophenotypes. Especially a thick contrast-enhancing margin seems to indicate a pro-inflammatory immune state. Via pioneering the integration of imaging and immunology, we not only advance basic glioblastoma science but we also open up novel avenues for research. In the future, e.g. patient stratification for therapy development could be based on imaging-guided immunophenotyping. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is the most frequent IgE-mediated disease, mainly in children and adolescents. Management of AR in the pediatric age may be heterogeneous, and the available guidelines do not adequately consider this issue. As a result, the Italian Society of Pediatric Allergy and Immunology (SIAIP) promoted a Delphi Consensus to define and evaluate the most relevant aspects of AR management in the pediatric setting in Italy. A qualified board of experts prepared a list of statements that a panel of Italian experts voted on using a web platform. Forty-two pediatricians participated. The results showed that all statements had consensus (> 80% of scores 4 + 5). In particular, there was awareness that AR is a type 2 inflammatory disease requiring adequate treatment. Topical drugs should be preferred, as they are better with cycles. Combined antihistamine/corticosteroid is also considered effective and safe in adolescents. In conclusion, AR deserves adequate attention and care. Current medications are safe and effective; treatment should be addressed to dampen type 2 inflammation and relieve complaints. [ABSTRACT FROM AUTHOR]

In the study, we assessed the effect on performance and health of a single injection of inorganic Se prepartum or feeding chicory silage and organic Se supplementation during the peripartum in ewes. Approximately one month before lambing, 45 pregnant Polypay ewes were moved into single pens and randomly assigned to 5 groups to be fed either grass or chicory silage and supplemented or not with 3.6 mg Se/day as selenium yeast or given a single prepartum injection of Na-selenite. Daily dry matter intake (DMI), water intake, milk production and components, blood metabolic, immune and inflammatory parameters, and blood micromineral levels were measured. DMI was lower in ewes fed chicory silage, although no statistical differences in milk yield were observed. Very few differences were observed in milk components, except fat %, which was higher among ewes fed chicory silage. The type of silage had a significant effect on the fatty acid profile of the milk, with the milk from ewes fed chicory having a higher proportion of unsaturated fatty acids and overall improved health indices compared to the milk from ewes fed grass silage. Blood NEFA and BHBA were higher in ewes fed chicory vs. grass silage. Neither silage type nor Se supplementation had a strong effect on most of the parameters associated with immune or inflammatory function, except for the liver enzymes GGT and GOT, which were lower, and a larger type I/type II ratio immune response measured by the DxD2 assay among ewes fed chicory vs. grass silage. No effects on parasite fecal egg counts were observed. Supplementation of ewes with Se-yeast resulted in higher blood levels of Se, whereas the one-time prepartum injection had no significant effect on whole blood Se levels. Feeding chicory silage and supplementing Se during the transition period had a minimal impact on ewe performance and health. [ABSTRACT FROM AUTHOR]

Summary Multiple myeloma (MM), one of the most frequent haematological malignancies, significantly increases the risk of bacterial infections due to treatment‐related side effects, comorbidities and cancer‐induced immune deficiencies. Recently, CD71+ erythroid cells (CECs) have been identified as key immunomodulators in neonates and cancer patients, but their role in MM progression remains unclear. Using a murine MM model, closely resembling human disease, we observed that MM progression is associated with anaemia and an increase in immature CECs, which are characterized by elevated arginase 2 (ARG2) expression. These MM‐associated CECs suppress T‐cell proliferation, contributing to impaired immune responses. Notably, ARG2 deficiency in mice led to slower MM progression and improved survival. Furthermore, MM‐bearing mice exhibited higher susceptibility to Listeria monocytogenes infections, mirroring the increased infection risk in MM patients. Our findings suggest that ARG2‐expressing CECs play a critical role in MM‐associated immune suppression and infection susceptibility, pointing out ARG2 as a potential therapeutic target to enhance immune function and reduce infection risks in MM patients. [ABSTRACT FROM AUTHOR]

Background and objectives: Currently, research on the role of B cells in esophageal cancer (EC) is limited, and existing studies on their impact are controversial. Therefore, this study was conducted to elucidate the complex causal relationship between B cells and EC, expand the understanding of esophageal cancer immunology. Methods: Bidirectional two-sample Mendelian randomization (MR) was performed to assess the causal relationships between 190 B cell phenotypes and EC. To complement the MR analysis, Bayesian Weighted Mendelian Randomization (BWMR) was employed, and sensitivity analyses were conducted to evaluate the robustness of the findings. Positive results were further validated in independent cohorts of esophageal cancer studies. In addition, RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) were utilized for validation, incorporating B cell-related gene expression analysis and functional enrichment analysis to support the MR findings. Results: In the primary analysis, significant causal relationships were observed between 5 B cell types and the risk of EC; the onset of EC was causally linked to 3 B cell phenotypes. Validation in other cohorts revealed that 4 outcomes aligned with the primary analysis, included were CD19 on IgD + CD38-, CD20 on IgD- CD27-, CD20 on IgD- CD38br, and CD38 on PB/PC. Further validation using RNA-seq data showed that CD38 mRNA was significantly overexpressed in EC tissues, whereas CD19 and MS4A1 mRNA levels did not differ significantly between tumor and normal tissues. Functional enrichment analysis revealed that CD19, MS4A1, and CD38 are involved in multiple tumor-related immune pathways, suggesting their pivotal role in regulating the tumor immune microenvironment. Conclusions: Our study suggests a potential connection between B cell phenotypes and EC through bidirectional two-sample MR combined with BWMR analysis, providing a preliminary basis for future research. [ABSTRACT FROM AUTHOR]

Context: Piglets encounter numerous challenges post-birth, and positive maternal influences can significantly aid their survival. Aims: This study aimed to investigate the potential impact of dietary fiber (DF) consumption during pregnancy on the establishment of colonic flora and immunity in offspring. Methods: Sixty-eight multiparous sows were randomly assigned to either a control diet lacking fiber sources or a diet supplemented with a fiber mixture. The study evaluated the developmental status, intestinal microecology, and immune indices, including the expression of Toll-like receptors and nuclear factor kappa-B, tumor necrosis factor α, interleukins 6 and 10, and interferon γ, as well as the concentrations of complement components 3 and 4, and immunoglobulins G and M in the offspring. Key results: The findings revealed a significant reduction in Toll-like receptor 4 and nuclear factor kappa-B messenger RNA levels in the colon and tumor necrosis factor α levels in the serum of 21-day-weaned piglets from the fiber group, indicating a decrease in inflammation. Moreover, there was a notable increase in the abundance of Roseburia and Lactobacillus in the colons of weaned piglets from the fiber-supplemented group, whereas Odoribacter showed a substantial decrease. This indicates that sows transfer beneficial microorganisms to their piglets, and fiber supplementation further enhances these positive microbial changes. Conclusion: This study highlights the positive impact on the microbiota profile and immunity of piglets of fiber supplementation in sow diets during pregnancy, using a 3% purified fiber mixture. These findings hold implications for the enhanced development of weaned piglets, providing valuable theoretical support. Piglets face many survival challenges after birth, and maternal beneficial influences can aid in their survival. This study found that supplementing a sow's diet during pregnancy with 3% purified fiber mixture could beneficially impact the piglets' microbiota profile and immunity. These results can provide some theoretical support for the subsequent better development of weaned piglets. [ABSTRACT FROM AUTHOR]

Spontaneous preterm birth (sPTB), defined as live birth before 37 weeks of gestational age, is associated with immune dysregulation and pro-inflammatory conditions that profoundly impact newborn health. The question of immune integrity at the maternal-foetal interface is a focus of recent studies centring not only sPTB but the conditions often affiliated with this outcome. Regulatory T cells (Tregs) play a critical anti-inflammatory role in pregnancy, promoting foetal tolerance and placentation. Due to this gestational role, it is hypothesised that decreased or dysfunctional Tregs may be implicated in cases of sPTB. This review examines studies comparing Treg presence in healthy term pregnancies and those with sPTB-associated conditions. Conflicting findings across different conditions and within sPTB itself have been identified. However, notable findings from the research indicate increased proinflammatory cytokines in pregnancies suffering from premature rupture of membranes (pPROM), chorioamnionitis, infection, preeclampsia, and gestational diabetes (GDM). Additionally, reduced Treg levels were identified in preeclampsia, GDM, and pPROM as well as chorioamnionitis presenting with increased Treg dysfunctionality. Treg deficiencies may contribute to health issues in preterm newborns. Current sPTB treatments are limited, underscoring the potential of in utero therapies targeting inflammation, including T cell interventions. Future research aims to establish consensus on the role of Tregs in sPTB and associated conditions and advancing understanding of mechanisms leading to Treg deficiencies in adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: The reactive enlargement of external iliac lymph nodes and increased blood flow in the infected region are commonly observed in lower limb infections. We aimed to differentiate between aseptic loosening and periprosthetic joint infection (PJI) after joint replacement surgery by quantifying the number of enlarged external iliac lymph nodes and using bone scintigraphy to monitor blood flow. Methods: We recruited 124 patients undergoing revision surgery for aseptic loosening or PJI. All the patients underwent preoperative dual-energy computed tomography (DECT) imaging for external iliac lymph nodes and bone scintigraphy. The diagnostic value was evaluated using ROC curve analysis. Results: The number of enlarged external iliac lymph nodes was significantly higher in the PJI group than in the aseptic failure group (4.0 versus. 1.0, p value < 0.001). The median affected/unaffected side ratio in the blood pool phase of ECT in the PJI group was 1.49, significantly higher than the aseptic failure group's median ratio of 1.04 (p value < 0.001). The AUC for diagnosing PJI using the number of enlarged lymph nodes alone was 0.91, and when using the bone scintigraphy blood pool phase alone, the AUC was 0.89. When both metrics were combined, the AUC increased to 0.95, which was higher than the AUCs for the ESR (AUC = 0.83), CRP (AUC = 0.76), and synovial fluid PMN% (AUC = 0.62). Conclusions: Combining the enlargement of the lymph node count with the bone scintigraphy blood pool phase is a promising approach for diagnosing PJI. [ABSTRACT FROM AUTHOR]

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout the process of liver metastases formation, immune cells play a pivotal role, particularly in the pre-metastatic and metastatic niches within the liver. Immune cells establish extensive and intricate interactions with tumor cells and other components in the liver, collectively promoting and sustaining the growth of liver metastases. Despite the limited efficacy of existing therapeutic modalities against some advanced liver metastases, novel immune-based treatment approaches are continuously being explored and validated. Building on the systematic elucidation of the immunosuppressive characteristics of liver metastases, we explored the potential of novel immunotherapies applicable to patients with liver metastases from multiple dimensions. [ABSTRACT FROM AUTHOR]

Immunology, a complex and rapidly evolving biological field, serves dual educational goals: training healthcare professionals and immunologists as well as promoting immune literacy among laypeople. This study conducted a scoping review of the literature to explore different aspects of immunology education, examining various contexts, levels, and content areas, including cognitive and motivational challenges. In addition, analysis covered different teaching strategies and research methodologies. Eight hundred and seventy-four articles were screened, and 20 articles proceeded to full-text analysis. Notably, the majority of the analysed studies concentrated on undergraduate education, emphasising strategies for teaching immunology, with a heavy reliance on quantitative research methods. Teaching strategies that were influential for improving the knowledge of the students were, for example, using games, using simulations and visualisations, using hands on experiments and self-directed learning. The content of the reviewed articles primarily revolved around topics related to innate and adaptive immunity, basic immunology, and immune system diseases. There was less emphasis on advanced immunology and on addressing the inherent complexity of the subject and even less on methods to motivate students to engage with immunology. Practical implications and suggestions for future research are described considering both healthcare practitioner training and immune literacy for laypeople. [ABSTRACT FROM AUTHOR]

Pathogen encounter can result in epigenetic remodeling that shapes disease caused by heterologous pathogens. Here, we examined innate immune memory in the context of commonly circulating respiratory viruses. Single-cell analyses of airway-resident immune cells in a disease-relevant murine model of SARS-CoV-2 recovery revealed epigenetic reprogramming in alveolar macrophages following infection. Post-COVID-19 human monocytes exhibited similar epigenetic signatures. In airway-resident macrophages, past SARS-CoV-2 infection increased activity of type I interferon (IFN-I)-related transcription factors and epigenetic poising of antiviral genes. Viral pattern recognition and canonical IFN-I signaling were required for the establishment of this innate immune memory and augmented secondary antiviral responses. Antiviral innate immune memory mounted by airway-resident macrophages post-SARS-CoV-2 was necessary and sufficient to ameliorate secondary disease caused by influenza A virus and curtailed hyperinflammatory dysregulation and mortality. Our findings provide insights into antiviral innate immune memory in the airway that may facilitate the development of broadly effective therapeutic strategies. [Display omitted] • Airway-resident macrophages (AMF) establish durable epigenetic memory post SARS2 • Chromatin loci of ISGs retain increased accessibility and are decorated with H3K4me1 • AMFs hyper-induce ISGs upon secondary antiviral recall responses • Innate immune memory in AMF ameliorates secondary influenza A virus disease The therapeutic potential of antigen-independent innate immune memory (IIM) is of particular relevance in the context of respiratory viruses with pandemic potential. Lercher et al. find that antiviral IIM in alveolar macrophages following SARS-CoV-2 infection ameliorates disease caused by a secondary unrelated pathogen, influenza A virus. [ABSTRACT FROM AUTHOR]

Rationale: The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)–associated pulmonary aspergillosis (CAPA) has yet to be explored. Objectives: To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. Methods: We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission. In addition, 16S rRNA gene sequencing data and viral and bacterial load of BAL samples from a subset of these patients, and of patients requiring noninvasive ventilation, were analyzed. We integrated 16S rRNA gene sequencing data with existing immune parameter datasets. Measurements and Main Results: Potential bacterial pathogens were detected in 20% (28/142) of patients with influenza and 37% (104/281) of patients with COVID-19, whereas aspergillosis was detected in 38% (54/142) of patients with influenza and 31% (86/281) of patients with COVID-19. A significant association between bacterial pathogens in BAL fluid and 90-day mortality was found only in patients with influenza, particularly patients with IAPA. Patients with COVID-19, but not patients with influenza, showed increased proinflammatory pulmonary cytokine responses to bacterial pathogens. Conclusions: Aspergillosis is more frequently detected in the lungs of patients with severe influenza than bacterial pathogens. Detection of bacterial pathogens associates with worse outcome in patients with influenza, particularly in those with IAPA, but not in patients with COVID-19. The immunological dynamics of tripartite viral–fungal–bacterial interactions deserve further investigation. [ABSTRACT FROM AUTHOR]

Located in Brisbane's Northshore riverfront precinct, just meters from the iconic Brisbane River, is the new Vaxxas Biomedical Facility. Dr Imogen Bermingham is a Principal Scientist in the Formulation and Analytical Team at Vaxxas, an Australian biotech company focused on developing a needle‐free vaccination technology. Here, we discuss her work at Vaxxas, highlighting the opportunities for translational research within the growing biotech industry landscape in Queensland, Australia. Dr Bermingham also reflects on her transition from academia to industry, leveraging her skill set and expanding her capabilities within the dynamic research environment at Vaxxas. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are prime therapeutic targets due to their pro-tumorigenic functions, but varying efficacy of macrophage-targeting therapies highlights our incomplete understanding of how macrophages are regulated within the tumor microenvironment (TME). The circadian clock is a key regulator of macrophage function, but how circadian rhythms of macrophages are influenced by the TME remains unknown. Here, we show that conditions associated with the TME such as polarizing stimuli, acidic pH, and lactate can alter circadian rhythms in macrophages. While cyclic AMP (cAMP) has been reported to play a role in macrophage response to acidic pH, our results indicate pH-driven changes in circadian rhythms are not mediated solely by cAMP signaling. Remarkably, circadian disorder of TAMs was revealed by clock correlation distance analysis. Our data suggest that heterogeneity in circadian rhythms within the TAM population level may underlie this circadian disorder. Finally, we report that circadian regulation of macrophages suppresses tumor growth in a murine model of pancreatic cancer. Our work demonstrates a novel mechanism by which the TME influences macrophage biology through modulation of circadian rhythms. Synopsis: Circadian rhythms of macrophages are altered by conditions associated with the tumor microenvironment, including acidic pH. This may be responsible for the heterogeneity in circadian clock gene expression within the tumor-associated macrophage population. Circadian rhythms of macrophages are altered by polarizing stimuli, acidic pH, and lactate. There is circadian disorder in the tumor-associated macrophage population. Heterogeneity of circadian rhythms and circadian gene expression within a population may underlie circadian disorder. The circadian clock in tumor-associated macrophages plays a tumor-suppressive role in pancreatic cancer. Circadian rhythms of macrophages are altered by conditions associated with the tumor microenvironment, including acidic pH. This may be responsible for the heterogeneity in circadian clock gene expression within the tumor-associated macrophage population. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax infection, when it occurs during pregnancy, has often been associated with serious adverse pregnancy outcomes. However, immunological alterations in pregnancy and their consequences have been little explored. We characterized the humoral immune response in pregnant women exposed to malaria by P. vivax antigens and its association with the maternal inflammatory profile and poor pregnancy outcomes. Methods: An observational cohort study in the Brazilian Amazon was conducted between 2013 and 2015. After applying exclusion criteria, 242 mother-child pairs were included in the analysis. Data on maternal infection, gestational outcomes, and inflammatory factors were evaluated in the maternal peripheral plasma. In samples from the first infection, the presence of total IgG and its subclasses in plasma against PvMSP119 protein were also quantified. Results: Previous exposure to malaria, observed by anti-total IgG antibodies to the PvMSP119 antigen, increased the inflammatory response to infection when the pregnant woman had malaria during pregnancy. IL-6 and IL-10 levels were positively correlated with parasitemia and with total IgG levels; but they were negatively correlated with the gestational age at delivery from Pv-infected woman. In multivariate linear regression analyses, IgG 1, 2 and 4 was negatively and positively associated with cytokines IL-6 and IL-10, respectively, in P. vivax-infection. Conclusions: An association between the humoral immune response and the peripheral inflammatory cytokine profile with the adverse outcomes in malaria in pregnancy by P. vivax was observed. Previous exposure to the parasite can influence the IL-6 and IL-10 response, which is associated with increased parasitemia, reduced maternal weight gain and premature delivery. Author summary: Plasmodium vivax malaria in pregnancy is also associated with several adverse outcomes, even in low-transmission regions such as South America. However, to our knowledge, no study has previously investigated the link between the humoral immune response due to previous exposure to P. vivax and the immunological profile during pregnancy infection and its association with poor pregnancy outcomes. In this study, after applying exclusion criteria, 242 mother-child pairs were evaluated for different immunological markers of malaria exposure in an endemic area in the Brazilian Amazon. We showed that previous exposure to P. vivax, through the humoral immune response to the PvMSP119 antigen, can exacerbate the inflammatory response during gestational malaria and is associated with increased parasitemia, reduced maternal weight gain and premature delivery. These findings help to understand the association between anti-PvMSP119 antibodies, considered exposure marker, and the maternal peripheral inflammatory profile throughout pregnancy, bringing important implications for understanding the immunobiology of the disease. [ABSTRACT FROM AUTHOR]

Bovine respiratory syncytial virus (BRSV) is a major respiratory pathogen in cattle and is relevant to the livestock industry worldwide. BRSV is most severe in young calves and is often associated with stressful management events. The disease is responsible for economic losses due to lower productivity, morbidity, mortality, and prevention and treatment costs. As members of the same genus, bovine and human RSV share a high degree of homology and are similar in terms of their genomes, transmission, clinical signs, and epidemiology. This overlap presents an opportunity for One Health approaches and translational studies, with dual benefits; however, there is still a relative lack of studies focused on BRSV, and the continued search for improved prophylaxis highlights the need for a deeper understanding of its immunological features. BRSV employs different host-immunity-escaping mechanisms that interfere with effective long-term memory responses to current vaccines and natural infections. This review presents an updated description of BRSV's immunity processes, such as the PRRs and signaling pathways involved in BRSV infection, aspects of its pathogeny, and the evading mechanisms developed by the virus to thwart the immune response. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is a powerful tool that can be used to specifically knock-down gene expression using double-stranded RNA (dsRNA) effector molecules. This approach can be used in aquaculture as an investigation instrument and to improve the immune responses against viral pathogens, among other applications. Although this method was first described in shrimp in the mid-2000s, at present, no practical approach has been developed for the use of dsRNA in shrimp farms, as the limiting factor for farm-scale usage in the aquaculture sector is the lack of cost-effective and simple dsRNA synthesis and administration procedures. Despite these limitations, different RNAi-based approaches have been successfully tested at the laboratory level, with a particular focus on shrimp. The use of RNAi technology is particularly attractive for the shrimp industry because crustaceans do not have an adaptive immune system, making traditional vaccination methods unfeasible. This review summarizes recent studies and the state-of-the-art on the mechanism of action, design, use, and administration methods of dsRNA, as applied to shrimp. In addition, potential constraints that may hinder the deployment of RNAi-based methods in the crustacean aquaculture sector are considered. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease for which remarkable therapeutic resistance is the norm. Conventional immunotherapies, like immune checkpoint inhibitors, show limited efficacy in PDA due to a remarkably immunosuppressive tumor microenvironment (TME) and systemic inflammation. This review discusses the potential of both exogenous and in situ vaccination strategies to overcome these barriers and enhance anti-tumor immunity in PDA. Exogenous vaccines, including whole-cell, dendritic cell, peptide, and nucleic acid-based vaccines, have shown varying degrees of promise but face challenges related to antigen selection, production complexities, and patient-specific factors. In contrast, in situ vaccination strategies leverage conventional cytotoxic therapies, such as chemotherapy and radiation therapy, to induce immunogenic cell death and modulate the TME with the aim to stimulate anti-tumor immunity. While preclinical studies support the use of in situ vaccination, balancing the stimulatory and inhibitory effects is likely fundamental to eliciting productive anti-tumor responses in patients. Ongoing research seeks to identify new innovative strategies that can harness the endogenous immune response and trigger in situ vaccination. Overall, while both vaccination approaches offer significant potential, further research and clinical trials will be needed to optimize these strategies for improving patient outcomes in PDA. [ABSTRACT FROM AUTHOR]

Most studies in comparative immunology involve investigations into the detailed mechanisms of the immune system of a nonmodel organism. Although this approach has been insightful, it has promoted a deep understanding of only a handful of species, thus inhibiting the recognition of broad taxonomic patterns. Here, we call for investigating the immune defenses of numerous species within a pointillist framework, that is, the meticulous, targeted collection of data from dozens of species and investigation of broad patterns of organismal, ecological, and evolutionary forces shaping those patterns. Without understanding basic immunological patterns across species, we are limited in our ability to extrapolate and/or translate our findings to other organisms, including humans. We illustrate this point by focusing predominantly on the biological scaling literature with some integrations of the pace of life literature, as these perspectives have been the most developed within this framework. We also highlight how the more traditional approach in comparative immunology works synergistically with a pointillist approach, with each approach feeding back into the other. We conclude that the pointillist approach promises to illuminate comprehensive theories about the immune system and enhance predictions in a wide variety of domains, including host-parasite dynamics and disease ecology. [ABSTRACT FROM AUTHOR]

Modified cholesterols such as oxidized low-density lipoprotein (OxLDL) contribute to atherosclerosis and other disorders through the promotion of foam cell formation and inflammation. In recent years, it has become evident that immune cell responses to inflammatory molecules such as OxLDLs depend on cellular metabolic functions. This review examines the known effects of OxLDL on immunometabolism and immune cell responses in atherosclerosis and several other diseases. We additionally provide context on the relationship between OxLDL and aging/senescence and identify gaps in the literature and our current understanding in these areas. [ABSTRACT FROM AUTHOR]

À l'occasion des états généraux de la médecine interne, le Collège National des Enseignants de Médecine Interne (CEMI) a mené une enquête sur l'activité d'enseignement, auprès de l'ensemble des hospitalo-universitaires (HU) de médecine interne français. L'enquête a été réalisée en septembre 2023 en adressant un courriel aux 101 professeurs des universités–praticiens hospitaliers (PU–PH) et 18 maîtres de conférence des universités–praticiens hospitaliers (MCU–PH) de médecine interne de la sous-section 53-01 du conseil national des universités (CNU), ainsi qu'aux 11 internistes HU émargeant en immunologie (sous-section 47-01) ou en thérapeutique (sous-section 48-04). Soixante-treize HU (56,1 %) ont répondu à l'enquête, dont 65 PU–PH, 7 MCU–PH et 1 praticien hospitalo-universitaire (PHU). Les HU de médecine interne participent à l'enseignement facultaire : 80 % sont responsables d'enseignement, 30 % sont responsables d'année ou de cycle ou animent des commissions et 40 % ont eu ou ont un mandat d'élu à la faculté ou à l'université. Les HU de médecine interne sont investis dans l'enseignement de la sémiologie médicale au cours du premier cycle des études de médecine, mais aussi dans les formations en maïeutique, sciences pharmaceutiques, odontologie et les formations paramédicales. Ils sont très investis dans la mise en place de la réforme du second cycle et 80 % interviennent dans la préparation des Examens Cliniques Objectifs Structurés (ECOS), essentiellement comme examinateurs (90 %). Ils participent également aux enseignements utilisant la simulation (60 %), à l'enseignement aux infirmiers de pratique avancée (IPA) (25 %), à la rédaction des ouvrages du CEMI (75 %). Huit (12 %) HU de médecine interne co-animent des formations avec des patients et 26 (38 %) participent à des enseignements en master à la faculté des sciences. Enfin, 94 % sont affiliés à une unité de recherche et 48 % encadrent des étudiants en thèse d'université. Les HU de médecine interne ont un fort engagement pédagogique, en particulier dans la sémiologie et dans la réforme du second cycle des études médicales avec les ECOS et la simulation. On the occasion of the General stage meeting of Internal Medicine, the National College of Internal Medicine Teachers (CEMI) conducted a survey on teaching activity among all French university hospital (HU) internal medicine specialists. The survey was carried out in September 2023 by sending an email to 101 hospital practitioners university professors (PU–PH) and 18 hospital practitioners assistant professors (MCU–PH) of internal medicine in subsection 53-01 of the National council of universities (CNU), as well as to the 11 HU internists working in immunology (subsection 47-01) or therapeutics (subsection 48-04). Seventy-three HUs (56.1%) responded to the survey, including 65 PU–PH, 7 MCU–PH and 1 university hospital practitioner (PHU). Internal medicine HUs participate in faculty teaching: 80% are responsible for teaching, 30% are responsible for the year or cycle or lead committees and 40% have had or have an elected mandate at the faculty or at university. Internal medicine HU are involved in the teaching of semiology during the first cycle of medical studies, but also in pharmaceutical sciences, dentistry, midwifery and in paramedical training. They are very invested in the implementation of the second cycle reform and 80% are involved in the preparation of Objective Structured Clinical Examinations (ECOS), mainly as examiners (90%). They also participate in teaching using simulation (60%), teaching advanced practice nurses (IPA) (25%), and writing CEMI books (75%). For ECOS, 90% participate as examiners, 60% participate in teaching using simulation, 25% are involved in teaching advanced practice nurses (IPA), 75% participated in the writing of CEMI works. Eight (12%) internal medicine HUs co-facilitate training with patients and 26 (38%) participate in master's courses at the Faculty of Sciences. Finally, 94% are affiliated with a research unit and 48% supervise university theses students. Internal medicine universities teachers have a strong educational commitment, particularly in semiology and in the reform of the second cycle of medical studies with ECOS and simulation. [ABSTRACT FROM AUTHOR]

Objective: Osteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in‐depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single‐cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease. Methods: Single cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP‐counter, and ssGSEA algorithms. Real‐time fluorescence quantitative PCR (RT‐qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults. Results: In OP samples, the proportions of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT‐qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65–0.90), immature B cells (0.76–0.92), and endothelial cells (0.79–0.87), while showing negative correlations with myeloid‐derived suppressor cells (negative 0.54–0.73), T follicular helper cells (negative 0.71–0.86), and natural killer T cells (negative 0.75–0.85). Conclusion: Neutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP. [ABSTRACT FROM AUTHOR]

Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC. Peripheral blood mononuclear cells isolated from blood collected from 23 patients with BC and 9 age‐matched unaffected‐by‐cancer control donors were assessed using a 21‐parameter flow cytometry panel composed of markers of T, B, natural killer and myeloid populations and immune checkpoint markers. Patients with BC had significantly lower numbers of circulating CD19+ B cells and elevated circulating CD4+CD8+ T cells compared with the control cohort. Immune checkpoint markers programmed cell death protein 1 (PD‐1) and T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3) were elevated in the total peripheral immune cell population in patients with BC. Within the BC cohort, PD‐1 expression in T and myeloid cells was elevated in muscle‐invasive compared with non–muscle‐invasive disease. In addition, elevated T, B and myeloid PD‐1 cell surface expression was significantly associated with tumor stage, suggesting that measures of peripheral immune cell exhaustion may be a predictor of tumor progression in BC. Finally, positive correlations between expression levels of the various immune checkpoints both overall and within key peripheral blood immune subsets collected from patients with BC were observed, highlighting likely coregulation of peripheral immune checkpoint expression. The peripheral blood immunophenotype in patients with BC is altered compared with cancer‐free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune‐targeted, personalized treatments. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is a debilitating neurodegenerative disease affecting the central nervous system, causing disability and life-threatening complications. The interplay between immune cells and signaling pathways is a topic for investigating novel therapies. Past research has shown how the Th1/Th2 ratio plays a key role in the pathogenesis of MS lesions. Modulating the Th1/Th2 ratios with an efficacious dietary supplement may improve some of the consequences of MS. Methods: Participants (n = 15) diagnosed with MS for an average of 12.4 years (standard deviation = 7.4; range = 2, 25) were enrolled in a clinical trial in which they consumed a dietary supplement regimen daily for 12 months. Venous blood was drawn at baseline and 12-month follow-up and peripheral blood mononuclear cells, cytokines, and growth factors were quantified. Infections, physical functioning, and quality of life were also assessed at baseline and 12 months. Results: The IL-2/IL-10 and IFN-γ/IL-10 ratios were significantly higher than those of the healthy adults, and while only IFN-γ/IL-10 increased significantly at 12 months, all ratios other than IFN-γ/TNF-α increased over the course of the intervention. The decrease in yeast infections was inversely correlated with IL-2/TNF-α and IFN-γ/TNF-α. Significant improvements in physical functioning and quality of life correlated with changes in the Th1/Th2 ratios in response to the dietary supplement regimen. Conclusions: The results show that dietary supplementation somewhat impacted the Th1/Th2 ratios over the course of the intervention (toward more Th1 dominance), and those changes were related to various clinical improvements of the participants' symptoms in cognitive, motor, and psychosocial dimensions. [ABSTRACT FROM AUTHOR]

Complications from general anesthesia, including pneumonia and decreased wound healing, are influenced by changes in immune cell function secondary to sedatives and anesthetics. It was hypothesized that immune cell function would be depressed in the early postanesthetic period. The objective was to investigate airway immune cell function before and after a general anesthetic episode in an equine in vivo model using ex vivo cell stimulations with lipopolysaccharide (LPS) for assessment of immune function. Prospective experimental study. Six healthy, adult, institution-owned horses. Each horse underwent a bronchoalveolar lavage (BAL) 3 days before and immediately after a 2 hour general anesthetic. The BAL fluid was examined for cytology, total nucleated cell count and isolation of immune cells. Airway immune cells were treated with LPS or media (control) for 6 hours and supernatant was analyzed via a commercially available immunoassay for cytokines [tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, IL-6, interferon gamma (IFNγ) and CXC motif chemokine ligand 8 (CXCL8)]. Data were compared using t -tests and Mann–Whitney tests. Before anesthesia (baseline), LPS stimulation induced a significant increase in all cytokines of interest, except CXCL8, versus control samples. Unstimulated cells, after an anesthetic episode, had a significant 1.8-fold increase in IL-1β (p = 0.029), and a significant decrease in IL-6 and TNFα (p = 0.028 and 0.033, respectively) versus baseline. Following anesthesia, stimulated cells had a significant decrease in IL-6 and TNFα (p = 0.037 and 0.042, respectively) versus baseline. This study supports the use of an equine in vivo model to assess airway immune cell function in relation to general anesthetic use. [ABSTRACT FROM AUTHOR]

A central issue in immunology is the immunological response against nonself. The prerequisite for a specific immunological response is the exposure to the immune system of a nonself antigen. Mathematical equations are presented, which define the fraction of all outcomes with a nonself allele in biallelic systems at the population level in pregnancy and transfusion/transplantation medicine. When designing assays, the mathematical descriptions can be used for estimating the number of genetic markers necessary to obtain a predetermined probability level in detecting nonself alleles of a given frequency. For instance, the equations can be helpful in the design of assays, where the nonself allele can be detected by analysis of cfDNA in plasma from pregnant women, to estimate fetal fraction or to monitor changes in cfDNA in plasma of transplantation patients. The equations give exact, quantitative descriptions of all nonself situations in pregnancy and transfusion/transplantation. [ABSTRACT FROM AUTHOR]

Cow's milk protein allergy (CMPA) affects 2% to 3% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding health care providers' (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices. This study utilized US HCPs' de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages. A total of 104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1's safety and effectiveness. Findings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care. [ABSTRACT FROM AUTHOR]

The intestinal immune system is the largest immune organ in the human body. Excessive immune response to intestinal cavity induced by harmful stimuli including pathogens, foreign substances and food antigens is an important cause of inflammatory diseases such as celiac disease and inflammatory bowel disease (IBD). Although great progress has been made in the treatment of IBD by some immune-related biotherapeutic products, yet a considerable proportion of IBD patients remain unresponsive or immune tolerant to immunotherapeutic strategy. Therefore, it is necessary to further understand the mechanism of immune cell populations involved in enteritis, including dendritic cells, macrophages and natural lymphocytes, in the steady-state immune tolerance of IBD, in order to find effective IBD therapy. In this review, we discussed the important role of innate and adaptive immunity in the development of IBD. And the relationship between intestinal immune system disorders and microflora crosstalk were also presented. We also focus on the new findings in the field of T cell immunity, which might identify novel cytokines, chemokines or anti-cytokine antibodies as new approaches for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Aim: Microbial colonization contributes to periodontitis and peri-implantitis with an increase in proinflammatory cytokines like IL 17. This has a vital role in the destructive process of tissue and bone around the implant. Type 2 diabetes mellitus has the potential to increase these microbial colonies thus becoming a risk factor. To compare and correlate the association of peri-implant sulcular microflora and salivary IL-17 between healthy and controlled diabetic individuals. Materials and Methods: A total of 30 participants who have undergone dental implant placement with screw-retained prosthesis were included in the study. Participants were divided into two groups, healthy (n = 15) and diabetic (n = 15). The subgingival plaque was collected from peri-implant sites into TE buffer vials and the salivary sample was collected into Eppendorf tubes at the 7th, 14th, and 30th day. Microbiological counts of P. gingivalis, T. denticola, T.forsythia, and F. nucleatum were evaluated by polymerase chain reaction, and salivary interleukin (IL)-17 levels were obtained by enzyme-linked immunosorbent assay. Results: The bacterial count was increased in both healthy and diabetic individuals but more prevalent in diabetes. The salivary IL-17 levels were increased in diabetic individuals which was statistically significant. Conclusion: Increased microbiota in both healthy and diabetic individuals along with increased IL-17 levels can lead to peri-implantitis which provides an insight into microbiological and immunological aspects in individuals with dental implants further acting as a predictor for peri-implantitis. [ABSTRACT FROM AUTHOR]

(1) Background: The importance of total eosinophil count in peripheral blood (EOS) as a type 2 inflammation marker is known to be fundamental in asthma, chronic sinusitis, and vasculitis. In cancer, despite their questionable antiproliferative effect, their role remains unclear. Our purpose was to describe the relationship between baseline blood EOS and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We retrospectively analyzed data from 137 adult patients who underwent surgical treatment for pancreatic ductal adenocarcinoma (PDAC) between the years 2012 and 2019. Patients with no recent history of systemic steroid use and without intraoperative metastases were included. Patients were categorized into two groups based on EOS (≥0.1 G/l and <0.1 G/l). Survival outcomes were analyzed using Cox proportional hazards regression models. (3) Results: According to EOS and PDAC stage, median OS values were as follows: in stage I–III, EOS ≥ 0.1 G/l group: 14.5 months, in stage I–III, EOS < 0.1 G/l group: 8.0 months, in stage IV, EOS ≥ 0.1 G/l group: 7.0 months, and in stage IV, EOS < 0.1 G/l group: 5.0 months. EOS < 0.1 G/l (vs. ≥0.1 G/l) was an independent prognostic factor for OS in both the uni- and multivariate Cox regression, respectively (HR = 1.48, p = 0.035 and HR = 1.57, p = 0.021). (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that type 2 inflammation may be the factor directly or indirectly lengthening the survival of patients with PDAC. [ABSTRACT FROM AUTHOR]

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a hyperinflammatory syndrome characterized by immune disorders. It is imperative to elucidate the immunophenotypic panorama and the interactions among these cells in patients. Human peripheral blood mononuclear cells were collected from healthy donors and sHLH patients and tested using multicolor flow cytometry. We used FlowSOM to explore and visualize the immunophenotypic characteristics of sHLH. By demonstrating the phenotypes of immune cells, we discovered that sHLH patients had significantly higher levels of CD56+ monocytes, higher levels of myeloid-derived suppressor cells, low-density neutrophil-to-T cell ratio, and higher heterogeneous T cell activation than healthy donors. However, natural killer cell cytotoxicity and function were impaired. We then assessed the correlations among 30 immune cell types and evaluated metabolic analysis. Our findings demonstrated polymorphonuclear myeloid-derived suppressor cells, CD56+ monocytes, and neutrophil-to-T cell ratio were elevated abnormally in sHLH patients, which may indicate an association with immune overactivation and inflammatory response. We are expected to confirm that they are involved in the occurrence of the disease through further in-depth research. [ABSTRACT FROM AUTHOR]

Background/Objectives: The COVID-19 pandemic reduced in-person pediatric visits in the United States by over 50%, while telehealth visits increased significantly. The national use of telehealth for children and the factors influencing their use have been rarely studied. This study aimed to investigate the prevalence of telehealth use during the COVID-19 pandemic and explore the potential factors linked to its use at the state level. Methods: A cross-sectional study of the National Survey of Children's Health (2021–22) sponsored by the federal Maternal and Child Health Bureau was performed. We used the least absolute shrinkage and selection operator (LASSO) regression to predict telehealth use during the pandemic. A bar map showing the significant factors from the multivariable regression was created. Results: Of the 101,136 children, 15.25% reported using telehealth visits due to COVID-19, and 3.67% reported using telehealth visits due to other health reasons. The Northeast states showed the highest telehealth use due to COVID-19. In the Midwest and Southern states, children had a lower prevalence of telehealth visits due to other health reasons. The LASSO regressions demonstrated that telehealth visits were associated with age, insurance type, household income, usual source of pediatric preventive care, perceived child health, blood disorders, allergy, brain injury, seizure, ADHD, anxiety, depression, and special needs. Conclusions: This study demonstrated significant variability in the use of telehealth among states during the COVID-19 pandemic. Understanding who uses telehealth and why, as well as identifying access barriers, helps maximize telehealth potential and improve healthcare outcomes for all. [ABSTRACT FROM AUTHOR]

Objective: Individuals with Down Syndrome (DS) exhibit a higher susceptibility to infections, suggesting potential immunological alterations within this population. Consequently, this study aims to assess the immune response profile in children with DS to identify potential immune dysfunctions associated with recurrent infections. Methods: The authors conducted a retrospective analysis involving 49 DS patients, examining various epidemiological, clinical, cytogenetic, and laboratory variables. The study's sample comprised patients aged 2-20 years, with a predominance of males. These patients were categorized into two groups based on the presence or absence of recurrent infections, as indicated by the Jeffrey Modell Foundation alert signs. Results: Immunoglobulin (Ig) A, G, and M levels were deemed normal, although individuals with DS experiencing recurrent infections exhibited significantly lower IgA levels. Additionally, CD3, CD4, CD8, and CD19 lymphocyte counts were found to be within normal ranges, with no significant differences between the two groups. While overall data indicated normal seroconversion levels of pneumococcal polysaccharide antibodies, a notable impairment in seroconversion was observed among DS patients with recurrent infections compared to those without such infections. Conclusion: The deficiency of anti-polysaccharide antibodies in individuals with DS may constitute an important immunological comorbidity. Therefore, it warrants further investigation, particularly among individuals with recurrent infections. [ABSTRACT FROM AUTHOR]

Introduction: The complex and unresolved pathogenesis of schizophrenia has posed significant challenges to its diagnosis and treatment. While recent research has established a clear association between immune function and schizophrenia, the causal relationship between the two remains elusive. Methods: We employed a bidirectional two-sample Mendelian randomization approach to investigate the causal relationship between schizophrenia and 731 immune cell traits by utilizing public GWAS data. We further validated the causal relationship between schizophrenia and six types of white cell measures. Results: We found the overall causal effects of schizophrenia on immune cell traits were significantly higher than the reverse ones (0.011 ± 0.049 vs 0.001 ± 0.016, p < 0.001), implying that disease may lead to an increase in immune cells by itself. We also identified four immune cell traits that may increase the risk of schizophrenia: CD11c+ monocyte %monocyte (odds ratio (OR): 1.06, 95% confidence interval (CI): 1.03~1.09, FDR = 0.027), CD11c+ CD62L-monocyte %monocyte (OR:1.06, 95% CI: 1.03~1.09, FDR = 0.027), CD25 on IgD+ CD38-naive B cell (OR:1.03, 95% CI:1.01~1.06, FDR = 0.042), and CD86 on monocyte (OR = 1.04, 95% CI:1.01~1.06, FDR = 0.042). However, we did not detect any significant causal effects of schizophrenia on immune cell traits. Using the white blood cell traits data, we identified that schizophrenia increases the lymphocyte counts (OR:1.03, 95%CI: 1.01-1.04, FDR = 0.007), total white blood cell counts (OR:1.02, 95%CI: 1.01-1.04, FDR = 0.021) and monocyte counts (OR:1.02, 95%CI: 1.00-1.03, FDR = 0.034). The lymphocyte counts were nominally associated with the risk of schizophrenia (OR:1.08,95%CI:1.01-1.16, P=0.019). Discussion: Our study found that the causal relationship between schizophrenia and the immune system is complex, enhancing our understanding of the role of immune regulation in the development of this disorder. These findings offer new insights for exploring diagnostic and therapeutic options for schizophrenia. [ABSTRACT FROM AUTHOR]

In the field of breast cancer treatment, the immunotherapy involving natural killer (NK) cells is increasingly highlighting its distinct potential and significance. Members of the interleukin (IL) family play pivotal regulatory roles in the growth, differentiation, survival, and apoptosis of NK cells, and are central to their anti-tumor activity. These cytokines enhance the ability of NK cells to recognize and eliminate tumor cells by binding to specific receptors and activating downstream signaling pathways. Furthermore, interleukins do not function in isolation; the synergistic or antagonistic interactions between different interleukins can drive NK cells toward various functional pathways, ultimately leading to diverse outcomes for breast cancer patients. This paper reviews the intricate relationship between NK cells and interleukins, particularly within the breast cancer tumor microenvironment. Additionally, we summarize the latest clinical studies and advancements in NK cell therapy for breast cancer, along with the potential applications of interleukin signaling in these therapies. In conclusion, this article underscores the critical role of NK cells and interleukin signaling in breast cancer treatment, providing valuable insights and a significant reference for future research and clinical practice. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) therapy has enabled a paradigm shift in Oncology, with the treatment of metastatic cancer in certain tumor types becoming akin to the treatment of chronic disease. Kidney transplant recipients (KTR) are at increased risk of developing cancer compared to the general population. Historically, KTR were excluded from ICI clinical trials due to concern for allograft rejection and decreased anti-tumor efficacy. While early post-marketing data revealed an allograft rejection risk of 40%-50%, 2 recent small prospective trials have demonstrated lower rates of rejection of 0%-12%, suggesting that maintenance immunosuppression modification prior to ICI start modulates rejection risk. Moreover, objective response rates induced by ICI for the treatment of advanced or metastatic skin cancer, the most common malignancy in KTR, have been comparable to those achieved by immune intact patients. Non-invasive biomarkers may have a role in risk-stratifying patients before starting ICI, and monitoring for rejection, though allograft biopsy is required to confirm diagnosis. This clinically focused review summarizes current knowledge on complications of ICI use in KTR, including their mechanism, risk mitigation strategies, non-invasive biomarker use, approaches to treatment of rejection, and suggestions for future directions in research. [ABSTRACT FROM AUTHOR]

Background: Neutrophils have long been consistently adjudged to hold a dominant position in acute inflammation, which once led people to undervalue their role in chronic malignancy. It is now acknowledged that neutrophils also infiltrate into the tumor microenvironment in substantial quantities and form a highly abundant immune population within the tumor, known as tumor-associated neutrophils (TANs). There has been a surge of interest in researching the eminent heterogeneity and plasticity of TANs in recent years, and scholars increasingly cotton on to the multifaceted functions of TANs so that strenuous endeavors have been devoted to enunciating their potential as therapeutic targets. Yet it remains much left to translate TAN-targeted immunotherapies into clinical practice. Therefore, there is great significance to comprehensively appraise the research status, focal point, and evolution trend of TAN by using bibliometric analysis. Methods: Publications related to TAN research from 2000 to 2024 are extracted from the Web of Science Core Collection. Bibliometric analysis and visualization were performed by tools encompassing Microsoft Excel, VOSviewer, CiteSpace, R-bibliometrix, and so on. Results: The bibliometric analysis included a total of 788 publications authored by 5291 scholars affiliated with 1000 institutions across 58 countries/regions, with relevant articles published in 324 journals. Despite China’s maximum quantity of publications and top 10 institutions, the United States is the leading country with the most high-quality publications and is also the global cooperation center. FRONTIERS IN IMMUNOLOGY published the most papers, whereas CANCER RESEARCH is the highest co-cited journal. Israeli professor Fridlender, Zvi G. is the founder, pioneer, and cultivator with the highest citation counts and H-index in the TAN area. Our analysis prefigures the future trajectories: TAN heterogeneity, neutrophil extracellular trap, the crosstalk between TANs and immunocytes, and immunotherapy will likely be the focus of future research. Conclusion: A comprehensive bibliometric and visual analysis is first performed to map the current landscape and intellectual structure of TAN, which proffers fresh perspectives for further research. The accurate identification of distinct TAN subpopulations and the precise targeting of key pro-tumor/anti-tumor subpopulations hold immense potential to develop into a TAN-targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Immune system and inflammation had a great influence on the progression of muscle atrophy. However, the causal relationship with specific immune cell traits remained uncertain. The aim of this study was to elucidate the genetic influences on these associations, providing insights into the underlying mechanisms of muscle atrophy. A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between immune cell phenotypes and muscle atrophy. Data on immune cell phenotypes were obtained from a research cohort containing data on 731 immune cell phenotypes and data on muscle atrophy were sourced from a Finnish database. MR analysis was performed using the MR-Egger method, weighted median, inverse variance weighting, heterogeneity testing, sensitivity analysis, and multiplicity analysis, with results subjected to false discovery rate(FDR) correction. Additionally, the UK Biobank cohort was utilized as an external validation. A total of 31 immune phenotypes with causal relationships with muscle atrophy were identified, including various phenotypes of conventional dendritic cells, myeloid cells, T cells/B cells/natural killer cells, regulatory cells, and T cell maturation stages. Among them, 12 immune phenotypes were identified as exhibiting a positive causal relationship with muscle atrophy, while 19 immune phenotypes were demonstrated to have a negative causal association, highlighting the complex interactions between immune cells and muscle health. The results of the reverse MR analysis indicated that a negative correlation between muscle atrophy and CD28 on secreting Treg (OR = 0.9038, 95%CI:0.8308 ~ 0.9832, P = 0.0186). A significant positive correlation was revealed by external datasets between the CD25 on IgD + CD38- immune phenotype and the risk of muscle atrophy, which was consistent with the trend observed in the training group (OR = 1.1041, 95% CI: 1.1005–1.1076, P = 0.0263). No evidence of pleiotropy was observed, and the reliability of these findings was demonstrated by the leave-one-out analysis. The findings highlight significant correlations between certain immune cell features and muscle atrophy, providing potential targets for further investigation of immunological mechanisms and therapeutic interventions for this condition. [ABSTRACT FROM AUTHOR]

ABSTRACT Canine cutaneous/subcutaneous soft‐tissue sarcomas (STS) are diversely derived mesenchymal neoplasms with a risk of recurrence and/or metastasis depending on the extent of surgical excision and histologic grade. Lymphoid aggregates (LAs) are often described in these tumours but not characterised. In humans, LA characterised as tertiary lymphoid structures (TLSs) improve the prognosis of many tumours, including sarcomas. We sought to determine if LA meeting a size criterion (> 700 cells) in canine sarcomas met the criteria of TLS and the overall prevalence of LA of any size. RNA expression in large LAs versus aggregate‐adjacent sarcoma tissue (AAS) was measured in laser capture microdissected tissue and compared to curl‐derived RNA from aggregate‐free sarcomas and lymph nodes. CD3, CD20, MUM‐1 and PNAd expressions were measured using immunohistochemistry. CD20 and CD3 mRNA were more highly expressed in LA versus AAS (13.8 fold, p = 0.0003 and 2.3 fold, p = 0.043). This was supported by the IHC findings. The large LAs were also enriched in chemokine RNA expression characteristic of TLS (CXCR5 5.8 fold, p < 00001, CCL19 3.68 fold, p = 0.0209, CCL21 6.87 fold, p = 0.0209 and CXCL13 2.68 fold, p = 0.0924). Plasma cells and high endothelial venules were identified in LA containing tumours but not in control tissue. Large LAs were present in 12% of tumours, and LA of any size in 30%. We conclude that large LAs in canine STS are consistent with TLS. [ABSTRACT FROM AUTHOR]

Meningoencephalitis of unknown origin (MUO) represents an umbrella term for inflammatory, non-infectious central nervous system (CNS) diseases in dogs. Current therapeutic approaches, involving long-term glucocorticosteroid use, often fail to provide adequate relief or cure, and the effectiveness of additional immunosuppressive medications remains uncertain. Future advancements in MUO treatment may benefit from patient-specific therapies, potentially enhancing treatment precision, efficacy, and minimizing side effects. However, significant challenges impede this progress, including ambiguity in MUO subtype classification, uncertainties regarding the autoimmune nature vs. infectious triggers, and the lack of reliable diagnostic biomarkers. Clinical heterogeneity and overlapping signs with other encephalopathies further complicate diagnosis and treatment. This review gives an overview about diagnostic findings and immunological features of MUO. It advocates for a more overall characterization of MUO by using a polythetic system to better characterize MUO subtypes, identify immunological treatment targets, and establish a conceptual foundation for future therapeutic trials. Addressing these themes may lead to more effective and less burdensome treatments, improving the quality of life for dogs afflicted with MUO and their owners. [ABSTRACT FROM AUTHOR]

Neurological complications, including encephalopathy and stroke, occur in a significant proportion of COVID-19 cases but viral protein is seldom detected in the brain parenchyma. To model this situation, we developed a novel lowinoculum K18-hACE2 mouse model of SARS-CoV-2 infection during which active viral replication was consistently seen in mouse lungs but not in the brain. We found that several mediators previously associated with encephalopathy in clinical samples were upregulated in the lung, including CCL2, and IL-6. In addition, several inflammatory mediations, including CCL4, IFNg, IL-17A, were upregulated in the brain, associated with microglial reactivity. Parallel in vitro experiments demonstrated that the filtered supernatant from SARS-CoV-2 virion exposed brain endothelial cells induced activation of uninfected microglia. This model successfully recreates SARS-CoV-2 virus-associated para-infectious brain inflammation which can be used to study the pathophysiology of the neurological complications and the identification of potential immune targets for treatment. [ABSTRACT FROM AUTHOR]

HBV infection is a key risk factor for the development and progression of hepatocellular carcinoma (HCC), a highly invasive tumor, and is characterized by its persistent immunosuppressive microenvironment. This review provides an in-depth analysis of HBV-related HCC and explores the interactions between neutrophils, natural killer cells, and dendritic cells, examining their roles in regulating tumor-associated macrophages and CD8+ T cells and shaping the tumor microenvironment. Two critical players in the immunosuppressive milieu of HBV-related HCC are CD8+ T cells and tumor-associated macrophages (TAMs). The study explores how TAMs, initially recruited to combat infection, transform, adopting a tumor-promoting phenotype, turning against the body, promoting tumor cell proliferation, suppressing anti-tumor immunity, and assisting in the spread of cancer. Meanwhile, CD8+ T cells, crucial for controlling HBV infection, become dysfunctional and exhausted in response to persistent chronic viral inflammation. The review then dissects how TAMs manipulate this immune response, further depleting CD8+ T cell functions through mechanisms like arginine deprivation and creating hypoxic environments that lead to exhaustion. Finally, it explores the challenges and promising therapeutic avenues that target TAMs and CD8+ T cells, either separately or in combination with antiviral therapy and personalized medicine approaches, offering hope for improved outcomes in HBV-related HCC. [ABSTRACT FROM AUTHOR]