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Extracellular vesicles (EVs) are nanosized particles released by nearly every cell type across all kingdoms of life. As a result, EVs are ubiquitously present in various human body fluids. Composed of a lipid bilayer, EVs encapsulate proteins, nucleic acids, and metabolites, thus playing a crucial role in immunity, for example, by enabling intercellular communication. More recently, there has been increasing evidence that EVs can also act as key regulators of allergic immune responses. Their ability to facilitate cell‐to‐cell contact and to transport a variety of different biomolecules enables active modulation of both innate and adaptive immune processes associated with allergic reactions. A comprehensive understanding of the intricate mechanisms underlying the interactions among allergens, immune cells, and EVs is imperative to develop innovative strategies for controlling allergic responses. This review highlights the recent roles of host cell‐ and bacteria‐derived EVs in allergic diseases, presenting experimental and clinical evidence that underscores their significance. Additionally, the therapeutic potential of EVs in allergy management is outlined, along with the challenges associated with targeted delivery and cargo stability for clinical use. Optimization of EV composition and targeting strategies holds promise for advancing translational applications and establishing EVs as biomarkers or safe therapeutics for assessing allergic reactions. For these reasons, EVs represent a promising avenue for advancing both our understanding and management of allergic immune processes. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) received worldwide attention over the past decade when outbreaks of the disease were found to be associated with severe neurological syndromes and congenital abnormalities. Unlike most other flaviviruses, ZIKV can spread through sexual and transplacental transmission, adding to the complexity of Zika pathogenesis and clinical outcomes. In addition, the spread of ZIKV in flavivirus-endemic regions, and the high degree of structural and sequence homology between Zika and its close cousin Dengue have raised questions on the interplay between ZIKV and the pre-existing immunity to other flaviviruses and the potential immunopathogenesis. The Zika epidemic peaked in 2016 and has affected over 80 countries worldwide. The re-emergence of large-scale outbreaks in the future is certainly a possibility. To date, there has been no approved antiviral or vaccine against the ZIKV. Therefore, continuing Zika research and developing an effective antiviral and vaccine is essential to prepare the world for a future Zika epidemic. For this purpose, an in-depth understanding of ZIKV interaction with many different pathways in the human host and how it exploits the host immune response is required. For successful infection, the virus has developed elaborate mechanisms to escape the host response, including blocking host interferon response and shutdown of certain host cell translation. This review provides a summary on the key host factors that facilitate ZIKV entry and replication and the mechanisms by which ZIKV antagonizes antiviral innate immune response and involvement of adaptive immune response leading to immunopathology. We also discuss how ZIKV modulates the host immune response during sexual transmission and pregnancy to induce infection, how the cross-reactive immunity from other flaviviruses impacts ZIKV infection, and provide an update on the current status of ZIKV vaccine development. [ABSTRACT FROM AUTHOR]

The immune system's role is much more than merely recognizing self vs. non-self and involves maintaining homeostasis and integrity of the organism starting from early development to ensure proper organ function later in life. Unlike other systems, the central nervous system (CNS) is separated from the peripheral immune machinery that, for decades, has been envisioned almost entirely as detrimental to the nervous system. New research changes this view and shows that blood-borne immune cells (both adaptive and innate) can provide homeostatic support to the CNS via neuroimmune communication. Neurodegeneration is mostly viewed through the lens of the resident brain immune populations with little attention to peripheral circulation. For example, cognition declines with impairment of peripheral adaptive immunity but not with the removal of microglia. Therapeutic failures of agents targeting the neuroinflammation framework (inhibiting immune response), especially in neurodegenerative disorders, call for a reconsideration of immune response contributions. It is crucial to understand cross-talk between the CNS and the immune system in health and disease to decipher neurodestructive and neuroprotective immune mechanisms for more efficient therapeutic strategies. [ABSTRACT FROM AUTHOR]

Radiation therapy is an essential component of cancer care, contributing up to 40% of curative cancer treatment regimens. It creates DNA double‐strand breaks causing cell death in highly replicating tumour cells. However, tumours can develop acquired resistance to therapy. The efficiency of radiation treatment has been increased by means of combining it with other approaches such as chemotherapy, molecule‐targeted therapies and, in recent years, immunotherapy (IT). Cancer‐cell apoptosis after radiation treatment causes an immunological reaction that contributes to eradicating the tumour via antigen presentation and subsequent T‐cell activation. By contrast, radiotherapy also contributes to the formation of an immunosuppressive environment that hinders the efficacy of the therapy. Innate immune cells from myeloid and lymphoid origin show a very active role in both acquired resistance and antitumourigenic mechanisms. Therefore, many efforts are being made in order to reach a better understanding of the innate immunity reactions after radiation therapy (RT) and the design of new combinatorial IT strategies focused in these particular populations. [ABSTRACT FROM AUTHOR]

Vaccinal prophylaxis is the most effective way to reduce incidence rates. However, the immune response developing after injection of most inactivated vaccines is insufficient when used without adjuvants. Special attention should be paid to the issue of immunoprophylaxis of high-risk patients with impaired immune status. Use of appropriate adjuvants during vaccination can optimize development of protective immunity in immunocompromised patients. Cytokines that regulate in vivo immune-response cascades to any antigenic stimulus and influence the development of an antigen-specific immune response can be considered as potential immunoadjuvants. The present review analyzes briefly studies of the immunoadjuvant properties of cytokines used to increase the effectiveness of regularly scheduled vaccines and those used for epidemic indications. [ABSTRACT FROM AUTHOR]

Evolving technologies and increasing understanding of human physiology over the past century have afforded our ability to intervene on human diseases using implantable bio-materials. These bio-electronic devices present a unique challenge through the creation of an interface between the native tissue and implantable bio-materials: the generation of host immune response surrounding such devices. While recent developments in cancer immunology seek to stimulate the immune system against cancer, successful long-term application of implantable bio-material devices need to durably minimize reactive immune processes at involved anatomical sites. Peripheral immune system response has been studied extensively for implanted bio-materials at various body sites. Examples include tooth composites (Gitalis et al., 2019), inguinal hernia repair (Heymann et al., 2019), and cardiac stents and pacemaker leads (Slee et al., 2016). Studies have also been extended to less well-studied immune reactivity in response to CNS neural-electronic implant devices. Recent technological advances in 2-Photon Laser Scanning Microscopy (2P-LSM) have allowed novel insights into in vivo immune response in a variety of tissue microenvironments. While imaging of peripheral tissues has provided an abundance of data with regards to immune cell dynamics, central nervous system (CNS) imaging is comparatively complicated by tissue accessibility and manipulation. Despite these challenges, the results of dynamic intravital neuro-immune imaging thus far have provided foundational insights into basic CNS biology. Utilizing a combination of intravital and ex vivo 2P-LSM, we have observed novel pathways allowing immune cells, stromal cells, cancer cells and proteins to communicate between the CNS parenchyma and peripheral vasculature. Similar to what has been reported in the intestinal tract, we have visualized myeloid cells extend dendritic processes across the blood brain barrier (BBB) into pial blood vessels. Furthermore, transient vessel leaks seen during systemic inflammation provide opportunities for cellular protein to be exchanged between the periphery and CNS. These insights provide new, visual information regarding immune surveillance and antigen presentation within the CNS. Furthermore, when combining intravital 2P-LSM and microfluidic devices complexed with mathematical modeling, we are gaining new insights into the intravascular behavior of circulating immune cells. This new knowledge into the basic mechanisms by which cells migrate to and interact with the CNS provide important considerations for the design of neuro-electronic biomaterials that have the potential to connect the peripheral-neural microenvironments into a unique, artificial interface.

Evolving technologies and increasing understanding of human physiology over the past century have afforded our ability to intervene on human diseases using implantable bio-materials. These bio-electronic devices present a unique challenge through the creation of an interface between the native tissue and implantable bio-materials: the generation of host immune response surrounding such devices. While recent developments in cancer immunology seek to stimulate the immune system against cancer, successful long-term application of implantable bio-material devices need to durably minimize reactive immune processes at involved anatomical sites. Peripheral immune system response has been studied extensively for implanted bio-materials at various body sites. Examples include tooth composites (Gitalis et al., 2019), inguinal hernia repair (Heymann et al., 2019), and cardiac stents and pacemaker leads (Slee et al., 2016). Studies have also been extended to less well-studied immune reactivity in response to CNS neural-electronic implant devices. Recent technological advances in 2-Photon Laser Scanning Microscopy (2P-LSM) have allowed novel insights into in vivo immune response in a variety of tissue microenvironments. While imaging of peripheral tissues has provided an abundance of data with regards to immune cell dynamics, central nervous system (CNS) imaging is comparatively complicated by tissue accessibility and manipulation. Despite these challenges, the results of dynamic intravital neuro-immune imaging thus far have provided foundational insights into basic CNS biology. Utilizing a combination of intravital and ex vivo 2P-LSM, we have observed novel pathways allowing immune cells, stromal cells, cancer cells and proteins to communicate between the CNS parenchyma and peripheral vasculature. Similar to what has been reported in the intestinal tract, we have visualized myeloid cells extend dendritic processes across the blood brain barrier (BBB) into pial blood vessels. Furthermore, transient vessel leaks seen during systemic inflammation provide opportunities for cellular protein to be exchanged between the periphery and CNS. These insights provide new, visual information regarding immune surveillance and antigen presentation within the CNS. Furthermore, when combining intravital 2P-LSM and microfluidic devices complexed with mathematical modeling, we are gaining new insights into the intravascular behavior of circulating immune cells. This new knowledge into the basic mechanisms by which cells migrate to and interact with the CNS provide important considerations for the design of neuro-electronic biomaterials that have the potential to connect the peripheral-neural microenvironments into a unique, artificial interface. [ABSTRACT FROM AUTHOR]

Vaccines remain one of the most important pillars in preventative medicine, providing protection against a wide array of diseases by inducing humoral and/or cellular immunity. Of the many possible candidate antigens for subunit vaccine development, carbohydrates are particularly appealing because of their ubiquitous presence on the surface of all living cells, viruses, and parasites as well as their known interactions with both innate and adaptive immune cells. Indeed, several licensed vaccines leverage bacterial cell-surface carbohydrates as antigens for inducing antigen-specific plasma cells secreting protective antibodies and the development of memory T and B cells. Carbohydrates have also garnered attention in other aspects of vaccine development, for example, as adjuvants that enhance the immune response by either activating innate immune responses or targeting specific immune cells. Additionally, carbohydrates can function as immunomodulators that dampen undesired humoral immune responses to entire protein antigens or specific, conserved regions on antigenic proteins. In this review, we highlight how the interplay between carbohydrates and the adaptive and innate arms of the immune response is guiding the development of glycans as vaccine components that act as antigens, adjuvants, and immunomodulators. We also discuss how advances in the field of synthetic glycobiology are enabling the design, engineering, and production of this new generation of carbohydrate-containing vaccine formulations with the potential to prevent infectious diseases, malignancies, and complex immune disorders. • Glycans play a role in nearly every aspect of innate and adaptive immunology. • Many licensed vaccines leverage bacterial cell-surface carbohydrates as antigens. • Many glycans are used as adjuvants that enhance immune responses. • Glycans are used as delivery systems that promote specific immune cell or tissues. • Glycans are used as dampeners that suppress undesired humoral immune responses. [ABSTRACT FROM AUTHOR]

One cause of sepsis is systemic maladaptive immune response of the host to bacteria and specifically, to Gram-negative bacterial outer-membrane glycolipid lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS activates the innate immune system via Toll-like receptor-4/myeloid differentiation factor-2 complex. Intracellularly, LPS is also sensed by the noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The minimal functional determinant for innate immune activation is the membrane anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold can enable, diminish, or abolish immune activation. Bacteria are known to modify their LPS structure during environmental stress and infection of hosts to alter cellular immune phenotypes. In this review, we describe how mass spectrometry-based structural analysis of endotoxin helped uncover major determinations of molecular pathogenesis. Through characterization of LPS modifications, we now better understand resistance to antibiotics and cationic antimicrobial peptides, as well as how the environment impacts overall endotoxin structure. In addition, mass spectrometry-based systems immunoproteomics approaches can assist in elucidating the immune response against LPS. Many regulatory proteins have been characterized through proteomics and global/targeted analysis of protein modifications, enabling the discovery and characterization of novel endotoxin-mediated protein translational modifications. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) is a contagious epizootic pathogen adversely affecting porcine industry in Asian and European countries. Till date, 8 serotypes and 24 genotypes of the virus have been reported. Few live attenuated virus vaccine studies have reported to provide complete protection against ASFV infection but biohazard concern still remain. Recombinant subunit antigens are capable of providing cellular and humoral immunity in porcine, but not a single vaccine has hit the market yet. In the present study, we attempted to use recombinant Salmonella Typhimurium JOL912 strain harboring ASFV antigens (rSal-ASFV) to investigate its immunostimulant effect in porcine. Post intramuscular administration, we observed significant increment in the levels of helper T cells, cytotoxic T cells, natural killer (NK) cells, and immunoglobulin (i.e. IgG, IgA, and IgM) levels in rSal-ASFV treated groups. Further RT-PCR analysis indicated the increased expression of MHC-I, MHC-II, CD80/86, NK cell receptors (NKp30, NKp44, and NKp46) and cytokines while ELIspot analysis revealed significant production of IFN-γ in rSal-ASFV treated groups. Taken together, we are able to demonstrate that rSal-ASFV could elicit a non-specific cellular as well as humoral immune response. However, additional antigen specific immunity data is needed to evaluate its efficacy. Intramuscular administration of rSal-ASFV was found to be safe and immunostimulant in nature without any side-effects and may serve as an excellent option for in-vivo antigen delivery in pigs. [Display omitted] • Recombinant Salmonella was used for administration of ASFV antigens. • Salmonella inoculation was safe, devoid of any side-effects with zero mortality. • Administration of recombinant Salmonella induced a non-specific immune response. • ELIspot assay revealed significant interferon (IFN-γ) secretion in treated groups. [ABSTRACT FROM AUTHOR]

Since its discovery 75 years ago, a wealth of knowledge has accumulated on the role of cardiolipin, the hallmark phospholipid of mitochondria, in bioenergetics and particularly on the structural organization of the inner mitochondrial membrane. A surge of interest in this anionic doubly-charged tetra-acylated lipid found in both prokaryotes and mitochondria has emerged based on its newly discovered signaling functions. Cardiolipin displays organ, tissue, cellular and transmembrane distribution asymmetries. A collapse of the membrane asymmetry represents a pro-mitophageal mechanism whereby externalized cardiolipin acts as an “eat-me” signal. Oxidation of cardiolipin's polyunsaturated acyl chains - catalyzed by cardiolipin complexes with cytochrome c . - is a pro-apoptotic signal. The messaging functions of myriads of cardiolipin species and their oxidation products are now being recognized as important intracellular and extracellular signals for innate and adaptive immune systems. This newly developing field of research exploring cardiolipin signaling is the main subject of this review. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum. [ABSTRACT FROM AUTHOR]

Elevated concentrations of Nt-pro-BNP were revealed in 11% of apparently healthy subjects aged 19-24 years and 22% of middle-aged (34-55 years) subjects. An increase in Nt-pro-BNP blood concentration was detected in 90% of patients with metabolic syndrome. Elevated levels of Nt-pro-BNP in peripheral blood occur with age. Higher concentrations of the peptide were revealed in women. Inhibition of lymphocytes proliferation and differentiation accompanied by increasing concentration of Nt-pro-BNP in blood is associated with a deficiency of the IL-2 level due to increased IL-10 concentration. Immunosuppressive effect of IL-10 declares itself at the level of innate immune reactions as a decrease in blood counts of naive CD45RA+ T lymphocytes, natural killer cells, T cells with adhesion receptor ( CD56+) and adhesion receptor ligand ( CD62L+). To prevent a loss of the intercellular pool, the effect of Nt-pro-BNP is activated. No statistically significant correlations between the increased Nt-pro-BNP concentration in blood and the content of serum IgM, IgG, IgA, IgE, IL-6, TNF-α, IFN-γ, CEC C1q, or С3d, as well as glucose, hemoglobin, transferrin, iron, or free fatty acids were revealed in apparently healthy subjects. [ABSTRACT FROM AUTHOR]

The spectrum of Clostridium difficile infections is highly variable, ranging from asymptomatic carriage to fatal colitis depending on the strain virulence and on the host, its gut microbiota and its immune response. After disruption of the gut microbiota, C. difficile pathogenesis can be divided into three steps: 1) contamination by spores and their germination; 2) multiplication of vegetative cells and intestinal colonization using colonization factors; 3) production of the toxins TcdA and TcdB, and for some strains, the binary toxin, which are responsible for the clinical signs. Three lines of defense counteract C. difficile . The first line is the epithelial barrier, which is breached by the toxins. Then, a rapid innate immune response follows, which forms the second line of defense. It provides very quick defense reactions against C. difficile but is non-specific and does not confer memory. C. difficile and its virulence factors, the toxins and colonization factors, induce a highly pro-inflammatory response, which can be either beneficial or harmful, but triggers the adaptive immunity as the third line of defense required to control the infectious process. Adaptive immunity provides a highly specific immune response against C. difficile with memory and long lasting immunity. The innate and adaptive immune responses against the toxins and surface components are analyzed as well as their role in disease susceptibility, severity and recurrences. [ABSTRACT FROM AUTHOR]

Effective drug selection is the current challenge in rheumatoid arthritis (RA). Treatment failure may follow different pathomechanisms and therefore require investigation of molecularly defined subgroups. In this exploratory study, whole blood transcriptomes of 68 treatment-naïve early RA patients were analyzed before initiating MTX. Subgroups were defined by serologic and genetic markers. Response related signatures were interpreted using reference transcriptomes of various cell types, cytokine stimulated conditions and bone marrow precursors. HLA-DRB4-negative patients exhibited most distinctive transcriptional differences. Preponderance of transcripts associated with phagocytes and bone marrow activation indicated response and transcripts of T- and B-lymphocytes non-response. HLA-DRB4-positive patients were more heterogeneous, but also linked failure to increased adaptive immune response. RT-qPCR confirmed reliable candidate selection and independent samples of responders and non-responders the functional patterning. In summary, genomic stratification identified different molecular pathomechanisms in early RA and preponderance of innate but not adaptive immune activation suggested response to MTX therapy. [ABSTRACT FROM AUTHOR]

The tight control of the innate and adaptive immune responses in the stomach mucosa during chronic Helicobacter pylori infection is of prime importance for the bacteria to persist and for the host to prevent inflammation-driven diseases. This review summarizes recent data on the roles of innate and adaptive immune responses during H. pylori/host interactions. In addition, the latest preclinical developments of H. pylori vaccines are discussed with a special focus on the clinical trial reported by Zeng et al., who provided evidence that oral vaccination significantly reduces the acquisition of natural H. pylori infection in children. [ABSTRACT FROM AUTHOR]

Oncolytic viruses represent a diverse class of replication competent viruses that curtail tumor growth. These viruses, through their natural ability or through genetic modifications, can selectively replicate within tumor cells and induce cell death while leaving normal cells intact. Apart from the direct oncolytic activity, these viruses mediate tumor cell death via the induction of innate and adaptive immune responses. The field of oncolytic viruses has seen substantial advancement with the progression of numerous oncolytic viruses in various phases of clinical trials. Tumors employ a plethora of mechanisms to establish growth and subsequently metastasize. These include evasion of immune surveillance by inducing up-regulation of checkpoint proteins which function to abrogate T cell effector functions. Currently, antibodies blocking checkpoint proteins such as anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) have been approved to treat cancer and shown to impart durable clinical responses. These antibodies typically need pre-existing active immune tumor microenvironment to establish durable clinical outcomes and not every patient responds to these therapies. This review provides an overview of published pre-clinical studies demonstrating superior therapeutic efficacy of combining oncolytic viruses with checkpoint blockade compared to monotherapies. These studies provide compelling evidence that oncolytic therapy can be potentiated by coupling it with checkpoint therapies. [ABSTRACT FROM AUTHOR]

Background: Arcobacter (A.) butzleri has been described as causative agent for sporadic cases of human gastroenteritis with abdominal pain and acute or prolonged watery diarrhea. In vitro studies revealed distinct adhesive, invasive and cytotoxic properties of A. butzleri. Information about the underlying immunopathological mechanisms of infection in vivo, however, are scarce. The aim of this study was to investigate the immunopathological properties of two different A. butzleri strains in a well-established murine infection model. Results: Gnotobiotic IL-10-/- mice, in which the intestinal microbiota was depleted by broad-spectrum antibiotic treatment, were perorally infected with two different A. butzleri strains isolated from a diseased patient (CCUG 30485) or fresh chicken meat (C1), respectively. Eventhough bacteria of either strain could stably colonize the intestinal tract at day 6 and day 16 postinfection (p.i.), mice did not exert infection induced symptoms such as diarrhea or wasting. In small intestines of infected mice, however, increased numbers of apoptotic cells could be detected at day 16, but not day 6 following infection with either strain. A strain-dependent influx of distinct immune cell populations such as T and B cells as well as of regulatory T cells could be observed upon A. butzleri infection which was accompanied by increased small intestinal concentrations of pro-inflammatory cytokines such as TNF, IFN-γ, MCP-1 and IL-6. Remarkably, inflammatory responses following A. butzleri infection were not restricted to the intestinal tract, given that the CCUG 30485 strain induced systemic immune responses as indicated by increased IFN-γ concentrations in spleens at day 6, but not day 16 following infection. Conclusion: Upon peroral infection A. butzleri stably colonized the intestinal tract of gnotobiotic IL-10-/- mice. The dynamics of distinct local and systemic inflammatory responses could be observed in a strain-dependent fashion pointing towards an immunopathogenic potential of A. butzleri in vivo. These results indicate that gnotobiotic IL-10-/- mice are well suited to further investigate the molecular mechanisms underlying arcobacteriosis in vivo. [ABSTRACT FROM AUTHOR]

Since initial reports, more than 25 years ago, that T cells recognize lipids in the context on non-polymorphic CD1 molecules, our understanding of antigen presentation to non-peptide-specific T cell populations has deepened. It is now clear that αβ T cells bearing semi-invariant T cell receptor, as well as subsets of γδ T cells, recognize a variety of self and non-self lipids and contribute to shaping immune responses via cross talk with dendritic cells and B cells. Furthermore, it has been demonstrated that small molecules derived from the microbial riboflavin biosynthetic pathway (vitamin B2) bind monomorphic MR1 molecules and activate mucosal-associated invariant T cells, another population of semi-invariant T cells. Novel insights in the biological relevance of non-peptide- specific T cells have emerged with the development of tetrameric CD1 and MR1 molecules, which has allowed accurate enumeration and functional analysis of CD1- and MR1-restricted T cells in humans and discovery of novel populations of semi-invariant T cells. The phenotype and function of non-peptide-specific T cells will be discussed in the context of the known distribution of CD1 and MR1 molecules by different subsets of antigen-presenting cells at steady state and following infection. Concurrent modulation of CD1 transcription and lipid biosynthetic pathways upon TLR stimulation, coupled with efficient lipid antigen processing, result in the increased cell surface expression of antigenic CD1–lipid complexes. Similarly, MR1 expression is almost undetectable in resting APC and it is upregulated following bacterial infection, likely due to stabilization of MR1 molecules by microbial antigens. The tight regulation of CD1 and MR1 expression at steady state and during infection may represent an important mechanism to limit autoreactivity, while promoting T cell responses to foreign antigens. [ABSTRACT FROM AUTHOR]

Until the discovery of leptin 20 years ago, adipose tissue was considered only as a fat storage organ, involved in the regulation of energy homeostasis. At present, it is well known that adipokines, being leptin the forerunner of this superfamily, may act in different biological processes, including inflammation and immunity. In this review, we have explored the recent evidence about the relationship between leptin and immune system, summarizing the most important findings related to the involvement of leptin in both innate and adaptive immune response. [ABSTRACT FROM AUTHOR]

Over the last 20 years it has become recognized that low-grade inflammation plays a role in cardiovascular disease. More recently, participation of the innate and the adaptive immune response in mechanisms that contribute to inflammation in cardiovascular disease has been reported in atherosclerosis and hypertension. Different subsets of lymphocytes and their cytokines are involved in vascular remodelling in hypertension, chronic kidney disease and heart disease. Effector T-cells include Th1 (interferon-γ -producing) and Th2 (interleukin-4 producing) lymphocytes, as well as Th17 (which produce interleukin-17) and T-suppressor lymphocytes such as Treg-cells (regulatory T-cells), which express the transcription factor Foxp3 (forkhead box P3) and participate respectively as pro- and anti-inflammatory cells. Pro-inflammatory T-lymphocytes participate in mechanisms of cardiovascular disease in part by mediating the effects of angiotensin II and mineralocorticoids. Involvement of immune mechanisms in cardiac, vascular and renal changes in hypertension has been demonstrated in many experimental models, an example being the Dahl-salt sensitive rat and the spontaneously hypertensive rat. How activation of immunity is triggered remains unknown, but neo-antigens could be generated by elevated blood pressure through damage-associated molecular pattern receptors or other mechanisms. Once activated, Th1 cells may contribute to blood pressure elevation by affecting the kidney, vascular remodelling of blood vessels directly via the effects of the cytokines produced or through their effects on perivascular fat. Treg-cells protect from blood pressure elevation by acting upon similar targets. Recent data suggests that participation of these mechanisms that have been demonstrated already in murine models also occurs in humans. These novel findings may open the way for new therapeutic approaches to improve outcomes in hypertension and cardiovascular disease in humans. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM) causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM. [ABSTRACT FROM AUTHOR]

Abstract: There is a permanent interaction amid the innate and adaptive immune systems that leads to a defensive immune response against pathogens and contributes substantially to self–nonself discrimination. Toll-like receptors (TLRs) are essential molecules of the innate immune system that stimulate numerous inflammatory pathways and harmonize systemic defense against a wide array of pathogens. In addition to identifying unique molecular patterns associated with various sections of pathogens, TLRs may also recognize a number of self proteins and endogenous nucleic acids. Several reports have indicated that inappropriate stimulation of the TLR pathway via endogenous or exogenous ligands in animal models or humans may lead to the induction and/or prolongation of autoimmune response and tissue injury. [Copyright &y& Elsevier]

Abstract: Salmonella Enteritidis mutants with deletions in phoP, fliC or phoPfliC were tested for their virulence and their ability to induce parameters of the innate and adaptive immunity in addition to their potential for serological differentiation between vaccinated, non-vaccinated and infected chickens. The double phoPfliC deletion mutant was sufficiently attenuated but not diminished in its capability to inhibit the caecal colonisation and systemic invasion of homologous Salmonella Enteritidis shortly after administration of the vaccine strain to very young chicks. Immunisation with the attenuated ΔphoPfliC mutant resulted in protective effects which were only slightly and insignificantly lower than after “immunisation” with a Salmonella wild-type strain, indicating the capability to induce an intense adaptive immune response and protection against Salmonella exposure in older chickens. The deletion in fliC enabled the effective the differentiation between immunised and infected chickens using a commercially available ELISA kit. The double phoPfliC deletion mutant of Salmonella Enteritidis might be a potential and promising live Salmonella vaccine candidate with novel characteristics for use in poultry. [Copyright &y& Elsevier]

STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of STAT3 in immune cells caused severe inflammation in response to pathogens. This review discusses the recent progress and suggests directions for the future research on this interesting molecule.Cell Research (2006) 16: 214–219. doi:10.1038/sj.cr.7310029; published online 13 February 2006 [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a common organism associated with bacterial keratitis primarily resulting from contact lens usage. Advances in our understanding of host innate and adaptive immune responses to experimental infection have been achieved using animal models, including inbred mouse models that are classed as resistant (cornea heals) vs. susceptible (cornea perforates). Evidence has shown that sustained IL-12-driven IFN-? production in dominant Th1 responder strains such as C57BL/6 (B6) contributes to corneal destruction and perforation. In contrast, in Th2-responder BALB/c mice, IL-18-driven IFN-? production regulates bacterial killing with less corneal destruction. IL-1 and chemotactic cytokines (e.g., MIP-2) recruit PMN to the cornea. The critical role of these cells in the innate immune response and their regulation after bacterial infection has been established. The studies provide a better understanding of the regulatory mechanisms that operate in the cornea after P. aeruginosa challenge, determining susceptibility vs. resistance to disease, and are consistent with long-term goals of providing targets for better treatment of disease. [ABSTRACT FROM AUTHOR]

A comparative approach is potentially useful for understanding the role of mammal innate immunity role in stimulating adaptive immunity as well as the relationship between these two types of immune strategies. Considerable progress has been made in the elucidation of the co-ordinated events involved in plant perception of infection and their mobilisation of defence responses. Although lacking immunoglobulin molecules, circulating cells, and phagocytic processes, plants successfully use pre-formed physical and chemical innate defences, as well as inducible adaptive immune strategies. In the present paper, we review some shared and divergent immune aspects present in both animals and plants. [Copyright &y& Elsevier]

Human respiratory syncytial virus (hRSV) infection brings a wide spectrum of clinical outcomes, from a mild cold to severe bronchiolitis or even acute interstitial pneumonia. Among the known factors influencing this clinical diversity, genetic background has often been mentioned. In parallel, recent evidence has also pointed out that an early infectious experience affects heterologous infections severity. Here, we analyzed the importance of these two host-related factors in shaping the immune response in pneumoviral disease. We show that a prior gammaherpesvirus infection improves, in a genetic background-dependent manner, the immune system response against a subsequent lethal dose of pneumovirus primary infection notably by inducing a systematic expansion of the CD8+ bystander cell pool and by modifying the resident alveolar macrophages (AMs) phenotype to induce immediate cyto/chemokinic responses upon pneumovirus exposure, thereby drastically attenuating the host inflammatory response without affecting viral replication. Moreover, we show that these AMs present similar rapid and increased production of neutrophil chemokines both in front of pneumoviral or bacterial challenge, confirming recent studies attributing a critical antibacterial role of primed AMs. These results corroborate other recent studies suggesting that the innate immunity cells are themselves capable of memory, a capacity hitherto reserved for acquired immunity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Metronomic chemotherapy is optimized with tuned drug doses and drug-free breaks. • Innate immunity can be just as essential in antitumor efficacy as adaptive. • Conventional maximum tolerated dose administration can often be immunosuppressive. • Optimal drug scheduling may vary based on drug mechanism/target and cancer type. • Metronomic chemotherapy may be delivered with current biomaterials for clinical ease. Metronomic chemotherapy has been shown to elicit anti-tumor immune response and block tumor angiogenesis distinct from that observed with maximal tolerated dose (MTD) therapy. This review delves into the mechanisms behind anti-tumor immunity and seeks to identify the differential effect of dosing regimens, including daily low-dose and medium-dose intermittent chemotherapy (MEDIC), on both innate and adaptive immune populations involved in observed anti-tumor immune response. Given reports of VEGF/VEGFR blockade antagonizing anti-tumor immunity, drug choice, dose, and selective delivery determined by advanced formulations/vehicles are highlighted as potential sources of innovation for identifying anti-angiogenic modalities that may be combined with metronomic regimens without interrupting key immune players in the anti-tumor response. Engineered drug delivery mechanisms that exhibit extended and local release of anti-angiogenic agents both alone and in combination with chemotherapeutic treatments have also been demonstrated to elicit a potent and potentially systemic anti-tumor immune response, favoring tumor regression and stasis over progression. This review examines this interplay between various cancer models, the host immune response, and select anti-cancer agents depending on drug dosing, scheduling/regimen, and delivery modality. [ABSTRACT FROM AUTHOR]

The idea that bacterial toxins are not only killers but also execute more sophisticated roles during bacteria–host interactions by acting as negotiators has been highlighted in the past decades. Depending on the toxin, its cellular target and mode of action, the final regulatory outcome can be different. In this review, we have focused on two families of bacterial toxins: genotoxins and pore-forming toxins, which have different modes of action but share the ability to modulate the host's immune responses, independently of their capacity to directly kill immune cells. We have addressed their immuno-suppressive effects with the perspective that these may help bacteria to avoid clearance by the host's immune response and, concomitantly, limit detrimental immunopathology. These are optimal conditions for the establishment of a persistent infection, eventually promoting asymptomatic carriers. This immunomodulatory effect can be achieved with different strategies such as suppression of pro-inflammatory cytokines, re-polarization of the immune response from a pro-inflammatory to a tolerogenic state, and bacterial fitness modulation to favour tissue colonization while preventing bacteraemia. An imbalance in each of those effects can lead to disease due to either uncontrolled bacterial proliferation/invasion, immunopathology, or both. [ABSTRACT FROM AUTHOR]

• Inactivated swine influenza virus and poly(I:C) based chitosan nanovaccine formulation. • Chitosan nanovaccine enhanced antigen specific HI titer and T-cell responses. • Th1 and Th2 cytokines mRNA expressions were increased by chitosan nanovaccine. • Chitosan nanovaccine reduced heterologous challenge virus load and lung pathology. To improve the innate and adaptive immune responses elicited by a killed/inactivated swine influenza virus antigen (KAg)-loaded chitosan nanoparticles (CS NPs-KAg), we used the adjuvant, poly(I:C). The formulated CS NPs-KAg and CS NPs-poly(I:C) had a net surface charge of +30.7 mV and +25.1 mV, respectively. The CS NPs-KAg was coadministered with CS NPs-poly(I:C) (chitosan nanovaccine) as intranasal mist. Vaccinations enhanced homologous (H1N2-OH10) and heterologous (H1N1-OH7) hemagglutination inhibition (HI) titers in both vaccinated and virus-challenged animals compared to the control soluble poly(I:C) vaccinated pigs. In addition, the chitosan nanovaccine induced the proliferation of antigen-specific IFNγ secreting T-helper/memory and γδ T cells compared to control poly(I:C) group; and an increased Th1 (IFNγ, IL-6 and IL-2) and Th2 (IL-10 and IL-13) cytokines mRNA expression in the tracheobronchial lymph nodes compared to lymphoid tissues obtained from pigs given commercial influenza vaccine. The virus load in nasal passages and microscopic lung lesions were partially reduced by both chitosan nanovaccine and commercial vaccine. The HA gene homology between the vaccine and challenge viruses indicated that the chitosan nanovaccine induced a cross-protective immune response. In conclusion, coadministration of CS NPs-poly(I:C) with CS NPs-KAg augmented the cross-reactive specific HI titers and the cell-mediated immune responses in pigs. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory results have been reported as well. With the aim of improving the understanding and awareness of the immunological events triggered by PDT, this review focuses on the immunological effects post-PDT, described in preclinical and clinical studies. The reviewed preclinical evidence indicates that PDT is able to elicit a local inflammatory response in the treated site, which can develop into systemic antitumor immunity, providing long-term tumor growth control. Nevertheless, this aspect of PDT has barely been explored in clinical studies. It is clear that further understanding of these events can impact the design of more potent PDT treatments. Based on the available preclinical knowledge, recommendations are given to guide future clinical research to gain valuable information on the immune response induced by PDT. Such insights directly obtained from cancer patients can only improve the success of PDT treatment, either alone or in combination with immunomodulatory approaches. [ABSTRACT FROM AUTHOR]