Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular importance of platelets has been ...attributed to their essential role in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism. Increasing knowledge on the platelets' role in the vasculature has led to many advances in understanding not only how platelets interact with the vessel wall but also how they convey changes in the environment to other circulating cells. In addition to their well-described hemostatic function, platelets are active participants in the immune response to microbial organisms and foreign substances. Although incompletely understood, the immune role of platelets is a delicate balance between its pathogenic response and its regulation of thrombotic and hemostatic functions. Platelets mediate complex vascular homeostasis via specific receptors and granule release, RNA transfer, and mitochondrial secretion that subsequently regulates hemostasis and thrombosis, infection, and innate and adaptive immunity.
The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses ...to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.
•SARS-CoV-2-specific antibodies are detected in COVID-19 convalescent subjects•Most COVID-19 convalescent individuals have detectable neutralizing antibodies•Cellular immune responses to SARS-CoV-2 are found in COVID-19 convalescent subjects•Neutralization antibody titers correlate with the numbers of virus-specific T cells.
In blood samples from COVID-19 convalescent subjects, Ni et al. have detected SARS-CoV-2-specific humoral and cellular immunity. Most subjects display serum neutralizing activities, which correlate with the numbers of virus-specific T cells.
Staphylococcus aureus can lead to chronic infections and abscesses in internal organs including kidneys, which are associated with the expansion of myeloid-derived suppressor cells (MDSCs) and their ...suppressive effect on T cells. Here, we developed a mathematical model of chronic S. aureus infection that incorporates the T-cell suppression by MDSCs and suggests therapeutic strategies for S. aureus clearance. A therapeutic protocol with heat-killed S. aureus (HKSA) was quantified in silico and tested in vivo. Contrary to the conventional administration of heat-killed bacteria as vaccination prior to infection, we administered HKSA as treatment in chronically infected hosts. Our treatment eliminated S. aureus in kidneys of all chronically S. aureus-infected mice, reduced MDSCs, and reversed T-cell dysfunction by inducing acute inflammation during ongoing, chronic infection. This study is a guideline for a treatment protocol against chronic S. aureus infection and renal abscesses by repurposing heat-killed treatments, directed by mathematical modeling.
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Model-driven quantified therapy protocol design against chronic Staphylococcus aureus infection•Treatment with heat-killed S. aureus eradicates S. aureus in vivo•Treatment induces acute inflammation during ongoing, chronic S. aureus infection•A proof-of-principle against renal S. aureus abscesses
Immunity
Probiotics confer immunological protection to the host through the regulation, stimulation, and modulation of immune responses. Researchers have shifted their attention to better understand the ...immunomodulatory effects of probiotics, which have the potential to prevent or alleviate certain pathologies for which proper medical treatment is as yet unavailable. It has been scientifically established that immune cells (T- and B-cells) mediate adaptive immunity and confer immunological protection by developing pathogen-specific memory. However, this review is intended to present the recent studies on immunomodulatory effects of probiotics. In the early section of this review, concepts of probiotics and common probiotic strains are focused on. On a priority basis, the immune system, along with mucosal immunity in the human body, is discussed in this study. It has been summarized that a number of species of Lactobacillus and Bifidobacterium exert vital roles in innate immunity by increasing the cytotoxicity of natural killer cells and phagocytosis of macrophages and mediate adaptive immunity by interacting with enterocytes and dendritic, Th1, Th2, and Treg cells. Finally, immunomodulatory effects of probiotics on proinflammatory and anti-inflammatory cytokine production in different animal models have been extensively reviewed in this paper. Therefore, isolating new probiotic strains and investigating their immunomodulatory effects on cytokine profiles in humans remain a topical issue.
Inflammatory bowel disease (IBD) is a complex genetic disease that is instigated and amplified by the confluence of multiple genetic and environmental variables that perturb the immune-microbiome ...axis. The challenge of dissecting pathological mechanisms underlying IBD has led to the development of transformative approaches in human genetics and functional genomics. Here we describe IBD as a model disease in the context of leveraging human genetics to dissect interactions in cellular and molecular pathways that regulate homeostasis of the mucosal immune system. Finally, we synthesize emerging insights from multiple experimental approaches into pathway paradigms and discuss future prospects for disease-subtype classification and therapeutic intervention.
Chloroplast immunity illuminated Littlejohn, George R.; Breen, Susan; Smirnoff, Nicholas ...
The New phytologist,
March 2021, Letnik:
229, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Summary
The chloroplast has recently emerged as pivotal to co‐ordinating plant defence responses and as a target of plant pathogens. Beyond its central position in oxygenic photosynthesis and primary ...metabolism – key targets in the complex virulence strategies of diverse pathogens – the chloroplast integrates, decodes and responds to environmental signals. The capacity of chloroplasts to synthesize phytohormones and a diverse range of secondary metabolites, combined with retrograde and reactive oxygen signalling, provides exquisite flexibility to both perceive and respond to biotic stresses. These processes also represent a plethora of opportunities for pathogens to evolve strategies to directly or indirectly target ‘chloroplast immunity’. This review covers the contribution of the chloroplast to pathogen associated molecular pattern and effector triggered immunity as well as systemic acquired immunity. We address phytohormone modulation of immunity and surmise how chloroplast‐derived reactive oxygen species underpin chloroplast immunity through indirect evidence inferred from genetic modification of core chloroplast components and direct pathogen targeting of the chloroplast. We assess the impact of transcriptional reprogramming of nuclear‐encoded chloroplast genes during disease and defence and look at future research challenges.
Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, ...where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c− patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways. Blunted CXCL1 production reduced neutrophil recruitment to the airways, thus limiting tissue immunopathology during infection. In parallel, diet-derived SCFAs boosted CD8+ T cell effector function by enhancing cellular metabolism. Hence, dietary fermentable fiber and SCFAs set an immune equilibrium, balancing innate and adaptive immunity so as to promote the resolution of influenza infection while preventing immune-associated pathology.
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•The fermentable fiber inulin and SCFAs protect against influenza-induced pathology•SCFAs alter hematopoiesis by increasing macrophage precursors in the bone marrow•SCFAs shape macrophage functionality to alleviate neutrophil-mediated tissue damage•SCFAs enhance CD8+ T cell functionality by altering their metabolism
Trompette et al. report that a diet rich in the fermentable fiber inulin and the associated metabolites—short-chain fatty acids—improve the response of mice to influenza infection by dampening deleterious immunopathology caused by neutrophils while enhancing anti-viral CD8+ T cell responses through a boost in T cell metabolism.
Interferon-λ (IFN-λ) acts on mucosal epithelial cells and thereby confers direct antiviral protection. In contrast, the role of IFN-λ in adaptive immunity is far less clear. Here, we report that mice ...deficient in IFN-λ signaling exhibited impaired CD8
T cell and antibody responses after infection with a live-attenuated influenza virus. Virus-induced release of IFN-λ triggered the synthesis of thymic stromal lymphopoietin (TSLP) by M cells in the upper airways that, in turn, stimulated migratory dendritic cells and boosted antigen-dependent germinal center reactions in draining lymph nodes. The IFN-λ-TSLP axis also boosted production of the immunoglobulins IgG1 and IgA after intranasal immunization with influenza virus subunit vaccines and improved survival of mice after challenge with virulent influenza viruses. IFN-λ did not influence the efficacy of vaccines applied by subcutaneous or intraperitoneal routes, indicating that IFN-λ plays a vital role in potentiating adaptive immune responses that initiate at mucosal surfaces.
Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been ...termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
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