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This study aimed to evaluate the effect of adding liquid extract of algae (Hypnea musciformis, Grateloupia acuminata, and Sargassum muticum) (HGS) and Magnesium oxide nanoparticles (MgO NPs) using this extract to rear water of Oreochromis niloticus, on improving culture water indices, growth performance, digestive enzyme, hemato-biochemical characters, immune, antioxidative responses, and resistance after challenged by Aeromonas hydrophila with specific refer to the potential role of the mixture in vitro as resistance against three strains bacteria (Aeromonas sobria, Pseudomonas fluorescens, P. aeruginosa) and one parasite (Cichlidogyrus tilapia). The first group represented control, HGS0, whereas the other group, HGS5, HGS10, and HGS15 mL−1 of liquid extract, as well as all groups with 7.5 μg mL−1 MgO-NPs added to culture water of O. niloticus, for 60 days. Data showed that increasing levels at HGS 10 and HGS15 mL−1 in to-culture water significantly enhanced growth-stimulating digestive enzyme activity and a significantly improved survival rate of O. niloticus after being challenged with A. hydrophila than in the control group. The total viability, coliform, fecal coliform count, and heavy metal in muscle partially decreased at HGS 10 and HGS15 mL−1 than in the control group. Correspondingly, the highest positive effect on hemato-biochemical indices was noticed at levels HGS 10 and HGS15 mL−1. Fish noticed an improvement in immune and antioxidant indices compared to control groups partially at HGS 10 and HGS15 mL−1. Interestingly, fish cultured in rearing water with the mixture provided downregulated the related inflammatory genes (HSP70, TNF, IL-1β, and IL-8) partially at HGS15 mL−1. In vitro, the mixture showed positive efficiency as an antibacterial and partially antiparasitic at HGS 10 and HGS15 mL−1. This study proposes utilizing a mixture of (HGS) and (MgO-NPs) with optimum levels of 10–15 mL-1 in cultured water to improve water indices, growth, health status, and increased resistance of O. niloticus against bacterial and parasitic infection.

Vertical transmission of Trypanosoma cruzi (T. cruzi) become a globalized health problem accounting for 22% of new cases of Chagas disease (CD). Congenital infection is now considered the main route of CD spread in non-endemic countries where no routine disease testing of pregnant women is implemented. The main mechanisms that lead to fetal infection by T. cruzi remain poorly understood. Mother-to-child transmission may occur when bloodstream trypomastigotes interact with the syncytiotrophoblasts (SYNs) that cover the placenta chorionic villi. These highly specialized cells function as a physical barrier and modulate immune responses against pathogen infections. To model the human placenta environment, we have previously used a three-dimensional (3D) cell culture system of SYNs that exhibits differentiation characteristics comparable to placental trophoblasts. Further, we have shown that 3D-grown SYNs are highly resistant to T. cruzi infection. In this work, we used RNA sequencing and whole transcriptome analysis to explore the immunological signatures that drive SYNs’ infection control. We found that the largest category of differentially expressed genes (DEGs) are associated with inflammation and innate immunity functions. Quantitative RT-PCR evaluation of selected DEGs, together with detection of cytokines and chemokines in SYNs culture supernatants, confirmed the transcriptome data. Several genes implicated in the Toll-like receptors signaling pathways were upregulated in 3D-grown SYNs. In fact, TLR2 blockade and TLR3/7 knockdown stimulated T. cruzi growth, suggesting that these molecules play a significant role in the host cell response to infection. Ingenuity Pathway Analysis of DEGs predicted the activation of canonical pathways such as S100 protein family, pathogen induced cytokine storm, wound healing, HIF1α signaling and phagosome formation after T. cruzi exposure. Our findings indicate that SYNs resist infection by eliciting a constitutive pro-inflammatory response and modulating multiple defense mechanisms that interfere with the parasite’s intracellular life cycle, contributing to parasite killing and infection control. [ABSTRACT FROM AUTHOR]

Vertical transmission of Trypanosoma cruzi (T. cruzi) become a globalized health problem accounting for 22% of new cases of Chagas disease (CD). Congenital infection is now considered the main route of CD spread in non-endemic countries where no routine disease testing of pregnant women is implemented. The main mechanisms that lead to fetal infection by T. cruzi remain poorly understood. Mother-to-child transmission may occur when bloodstream trypomastigotes interact with the syncytiotrophoblasts (SYNs) that cover the placenta chorionic villi. These highly specialized cells function as a physical barrier and modulate immune responses against pathogen infections. To model the human placenta environment, we have previously used a three-dimensional (3D) cell culture system of SYNs that exhibits differentiation characteristics comparable to placental trophoblasts. Further, we have shown that 3D-grown SYNs are highly resistant to T. cruzi infection. In this work, we used RNA sequencing and whole transcriptome analysis to explore the immunological signatures that drive SYNs’ infection control. We found that the largest category of differentially expressed genes (DEGs) are associated with inflammation and innate immunity functions. Quantitative RT-PCR evaluation of selected DEGs, together with detection of cytokines and chemokines in SYNs culture supernatants, confirmed the transcriptome data. Several genes implicated in the Toll-like receptors signaling pathways were upregulated in 3D-grown SYNs. In fact, TLR2 blockade and TLR3/7 knockdown stimulated T. cruzi growth, suggesting that these molecules play a significant role in the host cell response to infection. Ingenuity Pathway Analysis of DEGs predicted the activation of canonical pathways such as S100 protein family, pathogen induced cytokine storm, wound healing, HIF1α signaling and phagosome formation after T. cruzi exposure. Our findings indicate that SYNs resist infection by eliciting a constitutive pro-inflammatory response and modulating multiple defense mechanisms that interfere with the parasite’s intracellular life cycle, contributing to parasite killing and infection control.

BACKGROUND: It has been a consensus to use wound dressings to protect and promote wound healing after debridement, but now there is no ideal multifunctional dressing that can simulate the skin structure. Asymmetric dressings can mimic the skin structure to the greatest extent, resistant to infection, control the water vapor exchange and promote the efflux of exudate. Therefore, asymmetric dressings have a great potential to become a kind of ideal wound dressings. OBJECTIVE: To summarize the latest research progress and biological application of asymmetric dressings. METHODS: The literature search was performed in PubMed, Web of Science, CNKI and Wanfang databases, and the keywords were “asymmetric dressing, wound asymmetric membrane, wound asymmetric film” in Chinese and English. The articles were screened according to the inclusion and exclusion criteria. Finally, 53 articles were included for review. RESULTS AND CONCLUSION: Asymmetric dressings can simulate the structure of human skin, besides, its density hydrophobic layer can prevent invasion of external bacterium and control the exchange of water vapor. The hydrophilic layer is able to load and release the required drugs. The porous structure is conducive to cell proliferation and adhesion, thus promoting wound healing. The asymmetric characteristics do not significantly affect the physical properties of the asymmetric dressings, but these dressings are usually composed of multiple materials, resulting in better properties than single material. According to their structural characteristics, current asymmetric dressings can be divided into three types: single-layer modified asymmetric dressings, double-layer asymmetric dressings and gradient asymmetric dressings. In the future work, asymmetric dressings will be endowed with more and more intelligent functions and will be further developed as a potential ideal skin substitute, to solve the problems faced by traditional dressings in clinical application. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of adding liquid extract of algae (Hypnea musciformis, Grateloupia acuminata, and Sargassum muticum) (HGS) and Magnesium oxide nanoparticles (MgO NPs) using this extract to rear water of Oreochromis niloticus, on improving culture water indices, growth performance, digestive enzyme, hemato-biochemical characters, immune, antioxidative responses, and resistance after challenged by Aeromonas hydrophila with specific refer to the potential role of the mixture in vitro as resistance against three strains bacteria (Aeromonas sobria, Pseudomonas fluorescens, P. aeruginosa) and one parasite (Cichlidogyrus tilapia). The first group represented control, HGS0, whereas the other group, HGS5, HGS10, and HGS15 mL−1 of liquid extract, as well as all groups with 7.5 μg mL−1 MgO-NPs added to culture water of O. niloticus, for 60 days. Data showed that increasing levels at HGS 10 and HGS15 mL−1 in to-culture water significantly enhanced growth-stimulating digestive enzyme activity and a significantly improved survival rate of O. niloticus after being challenged with A. hydrophila than in the control group. The total viability, coliform, fecal coliform count, and heavy metal in muscle partially decreased at HGS 10 and HGS15 mL−1 than in the control group. Correspondingly, the highest positive effect on hemato-biochemical indices was noticed at levels HGS 10 and HGS15 mL−1. Fish noticed an improvement in immune and antioxidant indices compared to control groups partially at HGS 10 and HGS15 mL−1. Interestingly, fish cultured in rearing water with the mixture provided downregulated the related inflammatory genes (HSP70, TNF, IL-1β, and IL-8) partially at HGS15 mL−1. In vitro, the mixture showed positive efficiency as an antibacterial and partially antiparasitic at HGS 10 and HGS15 mL−1. This study proposes utilizing a mixture of (HGS) and (MgO-NPs) with optimum levels of 10–15 mL-1 in cultured water to improve water indices, growth, health status, and increased resistance of O. niloticus against bacterial and parasitic infection. • Seaweed mixture extract (HGS) and (MgO-NPs) synthesis (HGS) was added to cultured water as a natural agent of Nile tilapia. • Including blend improves growth, health status, and resistance against pathogenic. • Immune response and antioxidant activities were significantly improved with increasing blend levels. • Blend controlled the inflammatory and stress-associated genes of tilapia. • (HGS) and (MgO-NPs) with optimum 10 - 15 mL-1 levels in cultured water improve water indices. [ABSTRACT FROM AUTHOR]

The natural history of human immunodeficiency virus (HIV) infection is well understood. In most individuals sexually exposed to HIV, the risk of becoming infected depends on the viral load and on sexual practices and gender. However, a low percentage of individuals who practice frequent unprotected sexual intercourse with HIV‐infected partners remain uninfected. Although the systematic study of these individuals has made it possible to identify HIV resistance factors including protective genetic patterns, such epidemiological situations remain paradoxical and not fully understood. In vitro experiments have demonstrated that peripheral blood mononuclear cells (PBMCs) from HIV‐free, unexposed blood donors are not equally susceptible to HIV infection; in addition, PBMCs from highly exposed seronegative individuals are generally resistant to infection by primary HIV clinical isolates. We review the literature on permissiveness of PBMCs from healthy blood donors and uninfected hyperexposed individuals to sustained infection and replication of HIV‐1 in vitro. In addition, we focus on recent evidence indicating that the gut microbiota may either contribute to natural resistance to or delay replication of HIV infected individuals. [ABSTRACT FROM AUTHOR]

Human schistosomiasis, which is caused by schistosomes, is a zoonosis that is difficult to control because of the many reservoir hosts. However, Microtus fortis is the only mammal that is naturally resistant to Schistosoma japonicum infection known in China, in which S. japonicum growth and development were arrested on day 12, and the worms eliminated on day 20 post-infection. In this review, we present an overview of the established and purported mechanisms of resistance to S. japonicum infection in M. fortis in comparison to Rattus norvegicus, a semi-permissive host. Clarifying the mechanism of this efficient resistance can help us to better understand host-parasite interaction and to provide better methods to control schistosomiasis.

Human schistosomiasis, which is caused by schistosomes, is a zoonosis that is difficult to control because of the many reservoir hosts. However, Microtus fortis is the only mammal that is naturally resistant to Schistosoma japonicum infection known in China, in which S. japonicum growth and development were arrested on day 12, and the worms eliminated on day 20 post-infection. In this review, we present an overview of the established and purported mechanisms of resistance to S. japonicum infection in M. fortis in comparison to Rattus norvegicus , a semi-permissive host. Clarifying the mechanism of this efficient resistance can help us to better understand host-parasite interaction and to provide better methods to control schistosomiasis. [ABSTRACT FROM AUTHOR]

Penicillium digitatum is the main postharvest pathogen of citrus fruit. Although the inner fruit peel part (albedo) is less resistant than the outer part (flavedo) to P. digitatum, the global mechanisms involved in their different susceptibility remain unknown. Here, we examine transcriptome differences between both tissues at fruit harvest and in their early responses to infection. At harvest, not only was secondary metabolism, involving phenylpropanoids, waxes, and terpenoids, generally induced in flavedo vs. albedo, but also energy metabolism, transcription factors (TFs), and biotic stress-related hormones and proteins too. Flavedo-specific induced responses to infection might be regulated in part by ERF1 TF, and are related to structural plant cell wall reinforcement. Other induced responses may be related to H2O2, the synthesis of phenylpropanoids, and the stress-related proteins required to maintain basal defense responses against virulent pathogens, whereas P. digitatum represses some hydrolase-encoding genes that play different functions and auxin-responsive genes in this peel tissue. In infected albedo, the repression of transport and signal transduction prevail, as does the induction of not only the processes related to the synthesis of flavonoids, indole glucosinolates, cutin, and oxylipins, but also the specific genes that elicit plant immunity against pathogens.

Background Resistance to latent Mycobacterium tuberculosis (M.tb) infection, identified by persistently negative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA), after close contact with pulmonary tuberculosis (TB) patients has not been extensively characterized. Stability of this "resistance" beyond 2 years from exposure is unknown. Methods 407 of 657 eligible human immunodeficiency virus (HIV)-negative adults from a TB household contact study with persistently negative TST (PTST−) or with stable latent M.tb infection (LTBI) were retraced 9.5 years (standard deviation = 3.2) later. Asymptomatic retraced contacts underwent 3 IGRAs and follow-up TST, and their M.tb infection status classified as definite/possible/probable. Results Among PTST− with a definite classification, 82.7% were concordantly TST−/ quantiferon-TB Gold− (QFT−), and 16.3% converted to TST+/QFT+ LTBI. Among original LTBI contacts, 83.6% remained LTBI, and 3.9% reverted their TST and were QFT−. Although TST and QFT concordance was high (κ = 0.78), 1.0% of PTST and 12.5% of original LTBI contacts could not be classified due to discordant TST and QFT results. Epidemiological variables did not differ between retraced PTST− and LTBI contacts. Conclusion Resistance to LTBI, defined by repeatedly negative TST and IGRA, in adults who have had close contact with pulmonary TB patients living in TB-endemic areas, is a stable outcome of M.tb exposure. Repeated longitudinal measurements with 2 different immune assays and extended follow-up provide enhanced discriminatory power to identify this resister phenotype and avoid misclassification. Resisters may use immune mechanisms to control aerosolized M.tb that differ from those used by persons who develop "classic" LTBI. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major public health problem. Household contact studies identify children and adults along the spectrum from Mtb exposure to disease. In the Kawempe Community Health Study (conducted in Kampala, Uganda), 872 culture-confirmed pulmonary TB cases and their 2,585 contacts were enrolled during 2002--2012 and followed for up to 2 years each. Risk factors identified by time-to-event analysis for secondary TB differed among children, women, and men. Younger age (P = 0.0061), human immunodeficiency virus (HIV) (P = 0.0002), thinness (P = 0.01), absent bacille Calmette-Guérin vaccination (P = 0.002), and epidemiologic risk score (P < 0.0001) were risks for children. For women, risks were HIV (P < 0.0001), thinness (World Health Organization criteria; P < 0.0001), and epidemiologic risk score (P = 0.003). For men, HIV (P = 0.0007) and low body mass index (P = 0.008) resulted in faster progression to TB. Tuberculin skin testing (TST) identified contacts with Mtb infection and those with persistently negative TST. Risks for faster time to Mtb infection were identified, and included age (P = 0.0007), baseline TST induration (P < 0.0001), and epidemiologic risk score (P < 0.0001) only in children. Those with persistently negative TST comprised 10% of contacts but had no unique epidemiologic characteristics among adults. The burden of Mtb infection and disease is high in TB households, and risk factors for progression from exposure to infection and disease differ among children, women, and men. [ABSTRACT FROM AUTHOR]

Abstract Background Extreme weather events such as summer heat waves become more frequent owing to global climate change and are predicted to alter disease dynamics. This is because high temperatures can reduce host immune function. Predicting the impact of climate change on host-parasite interactions is, however, difficult as temperature may also affect parasite infective stages and other host characteristics determining the outcome of interaction. Methods Two experiments were conducted to investigate these phenomena in a Lymnaea stagnalis–Echinoparyphium aconiatum (Trematoda) interaction. In the first experiment, the effects of exposure of snails to experimental heat waves [maintenance at 25°C vs. 15°C (control)] with different durations (3 days, 7 days) on the infection success of parasite cercariae was examined. In the second experiment, the infection success was examined under similar conditions, while controlling for the possible temperature effects on cercariae and at least partly also for host physiological changes that take place rapidly compared to alterations in immune function (exposure to cercariae at intermediate 20°C). Results In the first experiment, increased infection success at 25°C was found independently of the duration of the heat wave. In the second experiment, increased infection success was found only in snails maintained at 25°C for 7 days, a treatment in which snail immune defence is known to be impaired. Conclusions These results suggest that the effects of host resistance in determining overall parasite infection success can be overridden by effects of temperature on parasite transmission stages and/or alterations in other host traits than immune defence.

We investigated whether a 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 (T-cell immunoglobulin and mucin domain 1), modulates susceptibility to HIV-1 infection. The polymorphism was genotyped in three case/control cohorts of HIV-1 exposed seronegative individuals (HESN) and HIV-1 infected subjects from Italy, Peru, and Colombia; data from a Thai population were retrieved from the literature. Across all cohorts, homozygosity for the short TIM-1 allele was more common in HESNs than in HIV-1 infected subjects. A meta-analysis of the four association analyses yielded a p value of 0.005. In vitro infection assays of CD4+ T lymphocytes indicated that homozygosity for the short allele is associated with lower rate of HIV-1 replication. These results suggest that the deletion allele protects from HIV-1 infection with a recessive effect. [ABSTRACT FROM AUTHOR]

Objective: MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression that play important roles in viral infections. Alterations of specific miRNAs are described in HIV infection, suggesting a role for miRNAs in pathogenesis of this disease. We verified whether a particular miRNA signature could be identified in natural resistance to HIV-1. Methods: Expression level of 84 miRNAs was analyzed by RTqPCR in plasma and unstimulated peripheral blood mononuclear cell (PBMC) of 30 seronegative individuals repeatedly exposed to HIV-1 (HESN), 30 HIV seropositive subjects (HIV+), and 30 healthy controls (HC). Results were confirmed by individual RT-qPCR in in vitro HIV-1-infected PBMC and in their cell culture medium. Dicer and Drosha expression was analyzed in basal PBMC. Results: Whereas Dicer and Drosha expression was comparable in HESN, HIV+ and HC, several miRNAs were upregulated both in HESN and HIV+ compared with HC. Furthermore, miRNA-29a and miR-223 were upregulated in both unstimulated PBMC and plasma of HESN alone; their expression was reduced upon in vitro HIV-1 infection of HESN PBMC indicating that, upon infection, they are secreted in the extracellular milieu. These results were confirmed by individual qPCR. Conclusions: Our studies demonstrate that HIV-1 exposure modifies miRNAs expression even in the absence of productive infection. Because those miRNAs that are specifically increased only in HESN have been known to reduce HIV-1 replication, their modulation could represent an important mechanism in resistance to HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background: The genetic bases of natural resistance to HIV-1 infection remain largely unknown. Recently, two genome-wide association studies suggested a role for variants within or in the vicinity of the CYP7B1 gene in modulating HIV susceptibility. CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses. We analyzed the frequency of two previously described CYP7B1 variants (rs6996198 and rs10808739) in three independent cohorts of HIV-1 infected subjects and HIV-1 exposed seronegative individuals (HESN). Findings: rs6996198 and rs10808739 were genotyped in three case/control cohorts of sexually-exposed HESN and HIV-1-infected individuals from Italy, Peru and Colombia. Comparison of the allele and genotype frequencies of the two SNPs under different models showed that the only significant difference was seen for rs6996198 in the Peruvian sample (nominal p = 0.048, dominant model). For this variant, a random-effect meta-analysis yielded non-significant results (dominant model, p = 0.78) and revealed substantial heterogeneity among cohorts. No significant effect of the rs10808739 allelic status on HIV-1 infection susceptibility (additive model, p = 0.30) emerged from the meta-analysis. Conclusions: Although our study had limited power to detect association due to the small sample size, comparisons among the three cohorts revealed very similar allelic and genotypic frequencies in HESN and HIV-1 positive subjects. Overall, these data indicate that the two GWAS-defined variants in the CYP7B1 region do not strongly influence HIV-1 infection susceptibility. [ABSTRACT FROM AUTHOR]

Tuberculosis and sarcoidosis are inflammatory diseases characterized by granulomas that may occur in any organ but are often found in the lung. The panoply of classical human leukocyte antigen (HLA) alleles associated with occurrence and/or severity of both diseases varies considerably across studies. This heterogeneity of results, due to variation in factors like ancestry and disease subphenotype, as well as the use of simple modeling strategies to elucidate likely complex relationships, has made conclusions about underlying commonalities difficult. Here we perform HLA association analyses in individuals of African ancestry, using a greater resolution to include subphenotypes of disease and employing more comprehensive analytical techniques. Using a novel application of nearest-neighbor feature selection to score allelic importance, we investigated HLA allele association with Mycobacterium tuberculosis exposure outcomes in the first analysis of both latent Mycobacterium tuberculosis infection and active disease compared with those who, despite long-term exposure to active index cases, have neither positive diagnostic tests nor display clinical symptoms. We also compared persistent to resolved sarcoidosis. This led to the identification of novel HLA associations and evidence of main effects and interaction effects. We found strikingly similar main effects and interaction effects at HLA-DRB1, -DQB1, and -DPB1 in those resistant to tuberculosis (either latent or active) and persistent sarcoidosis., (© 2022 Wiley Periodicals LLC.)

Background Extreme weather events such as summer heat waves become more frequent owing to global climate change and are predicted to alter disease dynamics. This is because high temperatures can reduce host immune function. Predicting the impact of climate change on host-parasite interactions is, however, difficult as temperature may also affect parasite infective stages and other host characteristics determining the outcome of interaction. Methods Two experiments were conducted to investigate these phenomena in a Lymnaea stagnalis- Echinoparyphium aconiatum (Trematoda) interaction. In the first experiment, the effects of exposure of snails to experimental heat waves [maintenance at 25°C vs. 15°C (control)] with different durations (3 days, 7 days) on the infection success of parasite cercariae was examined. In the second experiment, the infection success was examined under similar conditions, while controlling for the possible temperature effects on cercariae and at least partly also for host physiological changes that take place rapidly compared to alterations in immune function (exposure to cercariae at intermediate 20°C). Results In the first experiment, increased infection success at 25°C was found independently of the duration of the heat wave. In the second experiment, increased infection success was found only in snails maintained at 25°C for 7 days, a treatment in which snail immune defence is known to be impaired. Conclusions These results suggest that the effects of host resistance in determining overall parasite infection success can be overridden by effects of temperature on parasite transmission stages and/or alterations in other host traits than immune defence. [ABSTRACT FROM AUTHOR]

Seed quality may be affected by several factors, including permeability, color, and lignin content in the seed coat. This study aimed at evaluating influence of lignin content in the tegument of seed samples of six different soybean cultivars, in which half of each sample was inoculated with the fungus Aspergillus flavus, on the physical and physiological quality, and on the seed health, during 180 days storage period, under cold chamber with controlled conditions of temperature and RH. For that, at each interval of 60 days, samples were removed, and the physiological quality of these seeds was assessed by means of moisture and lignin contents; and by tests of seed health, germination, and electrical conductivity. The moisture content of seeds remained constant during all storage period. In the seed health test, it was found that inoculation was efficient, once the minimum incidence of the fungus in the inoculated seeds was 85%. In the germination test, there was a trend of reduction on percentage germination with the increase in storage period. However, there was an increase on electrical conductivity of seeds assessed. It was concluded that there is no interference of the lignin content in the seed coat on the resistance to infection by the fungus Aspergillus flavus, even after seed storage for a period of 180 days. [ABSTRACT FROM AUTHOR]

No method has been reported to predict, even approximately, the impact of mild-to-moderate changes in several immunological parameters on resistance to infection. The ability to make such predictions would be useful in risk assessment. In addition, equations that predict host resistance on the basis of changes in components of a complex biological system (the immune system) would fulfill one of the major goals of systems biology. In this study, multiple machine learning classification methods were used to predict the effects of a series of drugs and chemicals on host resistance to Listeria monocytogenes in mice on the basis of changes in several holistic immunological parameters. A data set produced under the sponsorship of the National Toxicology Program (NTP) was used in this study. The NTP data set was found to have a high percentage of missing data and to be noisy (probably due to the intrinsically stochastic nature of immune responses). Data preprocessing steps were used to mitigate these problems. In evaluating the machine learning classifiers, we first randomly partitioned the NTP data set into 10 subsets. Each time, we used nine subsets of the data to train the machine learning classifiers, and the remaining single subset to predict outcomes with regard to host resistance. This process was repeated until all 10 combinations of the 9-1 split of the subsets have been tested. The best of the classifiers predicted host resistance outcome correctly for 94.7% of cases, a result which indicates it is possible to identify mathematical expressions that will be useful for risk assessment and to establish a basis for systems immunology. [ABSTRACT FROM PUBLISHER]

Abstract: The clearance of apoptotic cells by phagocytes is a fundamental process during tissue remodeling and resolution of inflammation. In turn, the phagocytosis of apoptotic cells generates signals that suppress pro-inflammatory activation of macrophages. These events occur during the resolution phase of inflammation and therefore the malfunctioning of this process may lead to inflammation-related tissue damage. Here, we demonstrate that the calcium-binding protein S100A9, normally abundant in the cytoplasm of neutrophils and also released by apoptotic neutrophils, is involved in the suppression of macrophages after the uptake of apoptotic neutrophils. Both, spontaneous and induced production of inflammatory species (nitric oxide, hydrogen peroxide and TNF-α) as well as the phagocytic activity were inhibited when macrophages were in presence of apoptotic neutrophils, conditioned medium from neutrophil cultures or a peptide corresponding to the C-terminal region of S100A9 protein. On the other hand, macrophages kept in the conditioned medium of neutrophils that was previously depleted of S100A9 were shown to resume the activated status. Finally, we demonstrate that the calcium-binding property of S100A9 might play a role in the suppression process, since the stimulation of intracellular calcium release with ionomycin significantly reversed the effects of the uptake of apoptotic neutrophils in macrophages. In conclusion, we propose that S100A9 is a novel component of the regulatory mechanisms of inflammation, acting side-by-side with other suppressor factors generated upon ingestion of apoptotic cells. [Copyright &y& Elsevier]

Anecdotal evidence points to genetic variation in resistance of cattle to infection with Mycobacterium bovis, the causative agent of bovine tuberculosis (BTB), and published experimental evidence in deer and cattle suggests significant genetic variation in resistance and reactivity to diagnostic tests. However, such genetic variation has not been properly quantified in the United Kingdom dairy cattle population; it is possible that it exists and may be a factor influencing the occurrence of BTB. Using models based on the outcome of the process of diagnosis (ultimate fate models) and on the outcome of a single stage of diagnosis (continuation ratio models, herd test-date models), this study shows that there is heritable variation in individual cow susceptibility to BTB, and that selection for milk yield is unlikely to have contributed to the current epidemic. Results demonstrate that genetics could play an important role in controlling BTB by reducing both the incidence and the severity of herd breakdowns. [ABSTRACT FROM AUTHOR]

Summary: Susceptibility to HIV infection is widely different among individuals, and it is known that individuals can be identified who are repeatedly exposed to HIV but in whom neither infection nor disease are seen. The possibility that sheer luck is not the only determinant of this phenomenon begun to be considered in 1989 when it was reported that T cell responses to HIV proteins could be detected in antibody-negative sexual partners of known HIV-positive men. In this review we will summarize the body of knowledge that stemmed from that first observation. [Copyright &y& Elsevier]

The Solanum tuberosum clone G8107(1) is highly resistant to Potato leafroll virus (PLRV) accumulation following graft inoculation and to PLRV infection by aphids. In glasshouse/insectary experiments, plants were inoculated with viruliferous aphids ( Myzus persicae); infection was detectable in some inoculated leaves (by enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction) but not in petioles, stems or non-inoculated leaves of inoculated plants. Secondary infection in tuber-progeny plants of inoculated plants was rare in G8107(1) (detected in only one of 86 tuber-progeny plants of 24 inoculated plants), while universal in susceptible controls. This resistance did not break down when tuber sprouts were inoculated or when a more efficient M. persicae vector clone was used. Aphids were able to acquire and transmit PLRV infection from infected plants of G8107(1) to test plants but at a lower frequency than from the susceptible cv. Maris Piper. We suggest that an important element of the very strong resistance of this clone to PLRV infection is resistance to virus movement within leaves or from leaves to petioles, thus preventing spread to the rest of the plant. [ABSTRACT FROM AUTHOR]

In the conventional mouse model for cutaneous leishmaniasis involving infection with stationary phase Leishmania major promastigotes at the base of the tail, mice congenic for leishmaniasis resistance loci designated lmr1,2,3 cured their lesions more rapidly and laid down more ordered collagen fibres than the susceptible parental BALB/c mice, while the opposite was the case for the congenic mice carrying the susceptibility loci on the resistant C57BL/6 background. In that model, we showed that wound healing and not T cell responses played a major role in determining the resolution of skin infection. Here, we show a similar disease phenotype in the mouse model that mimics more closely the situation in humans, that is, strictly intradermal infection in the ear pinna with small numbers of metacyclic promastigotes. The data show that at the site of infection the innate and adaptive immune responses act in concert to clear parasites, and induce tissue repair and wound healing. Importantly, the data show that the host responses controlled by the lmr loci, which act locally to control infection in the skin, are distinct from the host responses operating systemically in the draining lymph node. [ABSTRACT FROM AUTHOR]

The article discusses a study which seeks to protect HIV-1 infected individuals in Cambodia. The objective of the study is to look for biological factors and specific antibodies that could fight against the infection. It considers 48 HIV-1 positive patients diagnosed as uninfected individuals who engaged in unprotected sex for 1 year and 49 with unexposed controls. It evaluates HIV antibodies, T-cell responses and cellular factors.

Water-filtered infrared A (wIRA), a special form of heat radiation with a high tissue penetration and with a low thermal load to the skin surface, is able, through thermal and non-thermal effects, to essentially improve even energetically specific factors of the wound healing. This has been proven by measurements. wIRA can considerably alleviate the pain and accelerate the wound healing or improve a stagnating wound healing and diminish an elevated wound secretion and inflammation both in acute wounds (prospective, randomised, controlled, double-blinded studies of the Surgical University Hospital Heidelberg after abdominal surgery, n=94, and of the Children Surgical Department Kassel in severely burned children, n=45) and in chronic wounds and in problem wounds (prospective, randomised, controlled study in Basel, n=40, and prospective study of the University Tromsø/Norway in Hillerød/Denmark with effortful thermographic follow-up, n=10, in both studies chronic venous lower leg ulcers) including infected wounds. A positive influence on the wound healing is particularly possible even without a disturbance of wound healing. In chronic wounds complete healings are achieved, which were not seen before. wIRA is contact-free, easily applied, without discomfort for the patient, with absent consumption of material and with a good effect in the depth, which is equivalent to the sun heat radiation on the earth in moderate climatic zones. The irradiation of the uncovered wound is carried out typically from a distance of approximately 25 cm with a wIRA radiator. Wound healing and resistance to infection (e.g. granulocyte function including antibacterial oxygen radical formation of the granulocytes) depend decisively on a sufficient energy supply (and on sufficient oxygen). The clinically good effect of wIRA on wounds and also on problem wounds and wound infections can be explained by the improvement of both the energy supply per time (increase of metabolic rate) and the oxygen supply (e.g. for the granulocyte function). Because of a thermal effect on the tissue wIRA causes an improvement in all three decisive factors oxygen partial pressure, tissue temperature and tissue blood flow. In addition there are also non-thermal effects of infrared A in the sense of a direct stimulation of cells and cellular structures with reactions of the cells. [ABSTRACT FROM AUTHOR]

Solute carrier family 11 member a1 (Slc11a1), formerly known as Nramp1/Ity/Lsh/Bcg, is a proton/divalent cation antiporter that regulates susceptibility to infectious and autoimmune disease. Here we review recent studies on (1) the role of Slc11a1 in iron metabolism and iron recycling in macrophages; (2) the use of mouse breeding and introgression of knockouts onto Slc11a1 congenic backgrounds for genes encoding the multiple pleiotropic functions associated with Slc11a1; and (3) associations/linkages of SLC11A1 with human disease and how these relate to functional promoter region polymorphisms. [Copyright &y& Elsevier]

It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr–driven lymphomas in transplant patients and Kaposi’s sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers. [ABSTRACT FROM AUTHOR]

Penicillium digitatum is the main postharvest pathogen of citrus fruit. Although the inner fruit peel part (albedo) is less resistant than the outer part (flavedo) to P. digitatum, the global mechanisms involved in their different susceptibility remain unknown. Here, we examine transcriptome differences between both tissues at fruit harvest and in their early responses to infection. At harvest, not only was secondary metabolism, involving phenylpropanoids, waxes, and terpenoids, generally induced in flavedo vs. albedo, but also energy metabolism, transcription factors (TFs), and biotic stress-related hormones and proteins too. Flavedo-specific induced responses to infection might be regulated in part by ERF1 TF, and are related to structural plant cell wall reinforcement. Other induced responses may be related to H2O2, the synthesis of phenylpropanoids, and the stress-related proteins required to maintain basal defense responses against virulent pathogens, whereas P. digitatum represses some hydrolase-encoding genes that play different functions and auxin-responsive genes in this peel tissue. In infected albedo, the repression of transport and signal transduction prevail, as does the induction of not only the processes related to the synthesis of flavonoids, indole glucosinolates, cutin, and oxylipins, but also the specific genes that elicit plant immunity against pathogens. [ABSTRACT FROM AUTHOR]

• Penicillium digitatum induces changes in PLD, PLC and PLA2 activities in oranges. • Of the different CsPLD genes, the fungus more strongly affected CsPLDγ and CsPLDζ. • CsNPC and CsPI-PLC genes participate in the citrus fruit- P. digitatum interaction. • ABA action lies upstream of phospholipase activity and specific encoding genes. We investigated whether phospholipases play a role in citrus fruit susceptibility to be infected by Penicillium digitatum, and whether a connection exists between hormone abscisic acid (ABA) and phospholipases in the citrus fruit- P. digitatum interaction. Changes in both the activity of enzymes PLD, PLC and PLA 2 and the expression of a set of genes encoding them in response to infection in Navelate (Citrus sinensis (L.) Osbeck) orange and its ABA-deficient mutant Pinalate, which is less resistant to infection, were compared. The results showed the activation of PLD and PLC in infected Navelate fruit before disease development, and this activation was attenuated in the mutant, which suggests that both enzymes play a protective role in citrus fruit to cope with P. digitatum infection and the participation of ABA in their regulation. The transcriptional analyses further demonstrated a differential activation of various phospholipases-encoding genes by the fungus. Of the CsPLD genes (CsPLDα, CsPLDβ, CsPLDδ, CsPLDγ, CsPLDζ), the fungus had a stronger effect on CsPLDγ and CsPLDζ. This is the first report to suggest the participation of a PLDζ isoform in the plant-microbe interaction, and to indicate that this gene may be modulated by ABA in response to infection. The results also revealed that the CsPLC isoforms encoding both non-specific PLC (NPC) and phosphoinositide-specific PLCs (PI-PLC) may participate in the citrus fruit- P. digitatum interaction, and that ABA action occurs upstream of CsPI-PLC gene activation in infected citrus fruit. The changes induced by the fungus in PLA 2 activity and gene expression were less relevant. [ABSTRACT FROM AUTHOR]

Predicting viral emergence is difficult due to the stochastic nature of the underlying processes and the many factors that govern pathogen evolution. Environmental factors affecting the host, the pathogen and the interaction between both are key in emergence. In particular, infectious disease dynamics are affected by spatiotemporal heterogeneity in their environments. A broad knowledge of these factors will allow better estimating where and when viral emergence is more likely to occur. Here, we investigate how the population structure for susceptibility-to-infection genes of the plant Arabidopsis thaliana shapes the evolution of Turnip mosaic virus (TuMV). For doing so we have evolved TuMV lineages in two radically different host population structures: (1) a metapopulation subdivided into six demes (subpopulations); each one being composed of individuals from only one of six possible A. thaliana ecotypes and (2) a well-mixed population constituted by equal number of plants from the same six A. thaliana ecotypes. These two populations were evolved for twelve serial passages. At the end of the experimental evolution, we found faster adaptation of TuMV to each ecotype in the metapopulation than in the well-mixed heterogeneous host populations. However, viruses evolved in well-mixed populations were more pathogenic and infectious than viruses evolved in the metapopulation. Furthermore, the viruses evolved in the demes showed stronger signatures of local specialization than viruses evolved in the well-mixed populations. These results illustrate how the genetic diversity of hosts in an experimental ecosystem favors the evolution of virulence of a pathogen. [ABSTRACT FROM AUTHOR]