ResearchPad - immunity https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Genes Encoding Recognition of the <i>Cladosporium fulvum</i> Effector Protein Ecp5 Are Encoded at Several Loci in the Tomato Genome]]> https://www.researchpad.co/article/elastic_article_11291 The molecular interactions between tomato and Cladosporium fulvum have been an important model for molecular plant pathology. Complex genetic loci on tomato chromosomes 1 and 6 harbor genes for resistance to Cladosporium fulvum, encoding receptor like-proteins that perceive distinct Cladosporium fulvum effectors and trigger plant defenses. Here, we report classical mapping strategies for loci in tomato accessions that respond to Cladosporium fulvum effector Ecp5, which is very sequence-monomorphic. We screened 139 wild tomato accessions for an Ecp5-induced hypersensitive response, and in five accessions, the Ecp5-induced hypersensitive response segregated as a monogenic trait, mapping to distinct loci in the tomato genome. We identified at least three loci on chromosomes 1, 7 and 12 that harbor distinct Cf-Ecp5 genes in four different accessions. Our mapping showed that the Cf-Ecp5 in Solanum pimpinellifolium G1.1161 is located at the Milky Way locus. The Cf-Ecp5 in Solanum pimpinellifolium LA0722 was mapped to the bottom arm of chromosome 7, while the Cf-Ecp5 genes in Solanum lycopersicum Ontario 7522 and Solanum pimpinellifolium LA2852 were mapped to the same locus on the top arm of chromosome 12. Bi-parental crosses between accessions carrying distinct Cf-Ecp5 genes revealed putative genetically unlinked suppressors of the Ecp5-induced hypersensitive response. Our mapping also showed that Cf-11 is located on chromosome 11, close to the Cf-3 locus. The Ecp5-induced hypersensitive response is widely distributed within tomato species and is variable in strength. This novel example of convergent evolution could be used for choosing different functional Cf-Ecp5 genes according to individual plant breeding needs.

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<![CDATA[Moving Pieces in Molecular Immunology]]> https://www.researchpad.co/article/elastic_article_8020 <![CDATA[The developing immune network in human prenatal skin]]> https://www.researchpad.co/article/elastic_article_7954 The immune system in skin is established early during development. Throughout development it continues to expand and diversify.

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<![CDATA[Respiratory microbiome and epithelial interactions shape immunity in the lungs]]> https://www.researchpad.co/article/elastic_article_7951 The respiratory epithelium provides a highly effective barrier acting as the first line of defence against potentially harmful environmental stimuli including microbes and allergens.

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<![CDATA[Regulation of barrier immunity and homeostasis by integrin‐mediated transforming growth factor <i>β</i> activation]]> https://www.researchpad.co/article/elastic_article_7950 TGF‐β is a crucial cytokine in regulation of the immune system, especially at barrier sites. Many cell types can produce TGF‐β, but always as an inactive complex that requires activating to be functional. This review highlights vital pathways that activate TGF‐β in the intestine, lung and skin, with a focus on how integrins control TGF‐β activity in a context‐specific manner.

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<![CDATA[Immunological fortification at our barrier organs: Protecting us as we age]]> https://www.researchpad.co/article/elastic_article_7948 Our barrier surfaces are fundamental in protecting us from the outside world and segregating key biological processes. The immunological fortifications found at these sites therefore possess many distinct qualities, which are discussed in Immunology's series of reviews on Barrier Immunity. Together these reviews showcase novel biological processes identified through the use of state‐of‐the‐art technologies, and specifically highlight how these change throughout our lives.

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<![CDATA[The liver as an immunological barrier redefined by single‐cell analysis]]> https://www.researchpad.co/article/elastic_article_7947 The liver is a front‐line immune tissue that plays a major role in the detection, capture and clearance of pathogens and foreign antigens entering the bloodstream through a highly specialized network of liver‐adapted immune cells. Mapping the immune resident compartment in the liver has been challenging because it requires multimodal single‐cell deep phenotyping approaches of often rare cell populations in difficult to access samples. Recently, emerging single‐cell technologies have been applied to the diverse array of immune cells present in murine and human livers, and here we summarize how they have advanced or redefined our understanding of the immunological barrier provided by the liver.

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<![CDATA[Digesting the crisis: autophagy and coronaviruses]]> https://www.researchpad.co/article/N14e3723f-733f-4d90-9494-31489cab3f33 Autophagy is a catabolic pathway with multifaceted roles in cellular homeostasis. This process is also involved in the antiviral response at multiple levels, including the direct elimination of intruding viruses (virophagy), the presentation of viral antigens, the fitness of immune cells, and the inhibition of excessive inflammatory reactions. In line with its central role in immunity, viruses have evolved mechanisms to interfere with or to evade the autophagic process, and in some cases, even to harness autophagy or constituents of the autophagic machinery for their replication. Given the devastating consequences of the current COVID-19 pandemic, the question arises whether manipulating autophagy might be an expedient approach to fight the novel coronavirus SARS-CoV-2. In this piece, we provide a short overview of the evidence linking autophagy to coronaviruses and discuss whether such links may provide actionable targets for therapeutic interventions.

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<![CDATA[A Novel HIV Vaccine Adjuvanted by IC31 Induces Robust and Persistent Humoral and Cellular Immunity]]> https://www.researchpad.co/article/5989dab9ab0ee8fa60badf30

The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31® facilitated immunoglobulin isotype switching, leading to the production of Env-specific IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with IC31® and alum followed by NYVAC-CN54 boost resulted in the formation and persistence of central and effector memory populations in the spleen and an effector memory population in the gut. Our data suggest that this regimen is promising and could improve the protection rate by eliciting strong and long-lasting humoral and cellular immune responses.

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<![CDATA[The many faces of the anti-COVID immune response]]> https://www.researchpad.co/article/N3bcfd6cc-63dc-4070-9b16-1b961946f8a4

This Perspective explores the contributions of the innate and adaptive immune systems to both viral control as well as toxicity during COVID-19 infections and offers suggestions to both understand and therapeutically modulate anti-COVID immunity.

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<![CDATA[Toxin-neutralizing antibodies elicited by naturally acquired cutaneous anthrax are elevated following severe disease and appear to target conformational epitopes]]> https://www.researchpad.co/article/N0733fdcc-4c39-44e4-82cd-032e69d54dbc

Understanding immune responses to native antigens in response to natural infections can lead to improved approaches to vaccination. This study sought to characterize the humoral immune response to anthrax toxin components, capsule and spore antigens in individuals (n = 46) from the Kayseri and Malatya regions of Turkey who had recovered from mild or severe forms of cutaneous anthrax infection, compared to regional healthy controls (n = 20). IgG antibodies to each toxin component, the poly-γ-D-glutamic acid capsule, the Bacillus collagen-like protein of anthracis (BclA) spore antigen, and the spore carbohydrate anthrose, were detected in the cases, with anthrax toxin neutralization and responses to Protective Antigen (PA) and Lethal Factor (LF) being higher following severe forms of the disease. Significant correlative relationships among responses to PA, LF, Edema Factor (EF) and capsule were observed among the cases. Though some regional control sera exhibited binding to a subset of the tested antigens, these samples did not neutralize anthrax toxins and lacked correlative relationships among antigen binding specificities observed in the cases. Comparison of serum binding to overlapping decapeptides covering the entire length of PA, LF and EF proteins in 26 cases compared to 8 regional controls revealed that anthrax toxin-neutralizing antibody responses elicited following natural cutaneous anthrax infection are directed to conformational epitopes. These studies support the concept of vaccination approaches that preserve conformational epitopes.

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<![CDATA[Immunity, the God-given weapon against infection]]> https://www.researchpad.co/article/N7c179e2b-b17a-496c-8efe-6d8d5e0c0e71 ]]> <![CDATA[Discovery and Selection of Hepatitis B Virus-Derived T Cell Epitopes for Global Immunotherapy Based on Viral Indispensability, Conservation, and HLA-Binding Strength]]> https://www.researchpad.co/article/Naedb8cf7-7629-46b5-97fd-edfd6841c03e

Multiple HBV-derived T cell epitopes have been reported, which can be useful in a therapeutic vaccination strategy. However, these epitopes are largely restricted to HLA-A*02, which is not dominantly expressed in populations with high HBV prevalence. Thus, current epitopes are falling short in the development of a global immunotherapeutic approach. Therefore, we aimed to identify novel epitopes for 6 HLA supertypes most prevalent in the infected population. Moreover, established epitopes might not all be equally effective as they can be subject to different levels of immune escape. It is therefore important to identify targets that are crucial in viral replication and conserved in the majority of the infected population. Here, we applied a stringent selection procedure to compose a combined overview of existing and novel HBV-derived T cell epitopes most promising for viral eradication. This set of T cell epitopes now lays the basis for the development of globally effective HBV antigen-specific immunotherapies.

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<![CDATA[Genetic Determinants of Altered Virulence of Type O Foot-and-Mouth Disease Virus]]> https://www.researchpad.co/article/N4b83c25a-7a72-4ca7-a0e7-a6fd11103b0d

FMD is probably the most important livestock disease in the world due to the severe economic consequences caused. The alteration of several viral genes may give the virus selective advantage to maintain its prevalence in nature. Here, we identified that a 70-nucleotide deletion in the S fragment combined with a single leucine insertion in the leader protein (Lpro) is a novel determinant of restricted growth on bovine cells, which significantly contributes to the altered virulence of serotype O FMDV in cattle. A synergistic and additive effect of the 70-nucleotide deletion in the S fragment and the single leucine insertion in Lpro on the virulence and host specificity of the virus was determined. These results will benefit efforts to understand the vial pathogenicity mechanism and molecular characteristics of FMDV.

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<![CDATA[Hemagglutinin and Neuraminidase Antibodies Are Induced in an Age- and Subtype-Dependent Manner after Influenza Virus Infection]]> https://www.researchpad.co/article/Nbefbf6bf-957c-42fe-a3f6-de91c03c5afa

Data on the immunologic responses to neuraminidase (NA) is lacking compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and NA antibodies after infection is influenced by age and subtypes. Such response dynamics suggest the influence of immunological memory, and understanding how this process is regulated will be critical to any vaccine effort targeting NA immunity.

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<![CDATA[An adaptable defense]]> https://www.researchpad.co/article/Ncf24e325-dced-47b7-a6c8-7133e3262303

The response of bacteria to the threat posed by phages depends on their local environment.

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<![CDATA[LCMV‐specific CD4 T cell dependent polyclonal B‐cell activation upon persistent viral infection is short lived and extrafollicular]]> https://www.researchpad.co/article/N7bfe6a84-46ca-47a9-b1fd-83c5afa1cc7d

Abstract

Persistent virus infections with non‐ or poorly cytopathic viruses are commonly associated with B cell dysregulations. These include the induction of hypergammaglobulinemia and the emergence of virus‐unspecific antibodies. These seemingly unspecific antibody responses interfere with the virus‐specific humoral immunity and contribute to delayed virus control. Whether these virus‐unspecific antibodies are induced in the B cell follicle or at extrafollicular sites and whether one specific CD4 T cell subset is involved in the polyclonal B cell activation is unclear. Here we studied virus‐unrelated IgG antibody responses against self or foreign antigens in the context of persistent lymphocytic choriomeningitis virus (LCMV) infection. We found that the LCMV‐unspecific antibody response is short‐lived and induced predominantly at extrafollicular sites and depends on the presence of LCMV‐specific CD4 T cells. Our data support a scenario in which activated, virus‐specific CD4 T cells provide help to non‐specific B cells at extrafollicular sites, supporting the production of virus unspecific IgG antibodies during persistent viral infection.

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<![CDATA[CD28 and CD57 define four populations with distinct phenotypic properties within human CD8+ T cells]]> https://www.researchpad.co/article/N39c97f78-1bbd-4a39-9302-6ec308c02512

Abstract

After repeated antigen exposure, both memory and terminally differentiated cells can be generated within CD8+ T cells. Although, during their differentiation, activated CD8+ T cells may first lose CD28, and CD28 cells may eventually express CD57 as a subsequent step, a population of CD28+CD57+(DP) CD8+ T cells can be identified in the peripheral blood. How this population is distinct from CD28CD57(DN) CD8+ T cells, and from the better characterized non‐activated/early‐activated CD28+CD57 and senescent‐like CD28CD57+ CD8+ T cell subsets is currently unknown. Here, RNA expression of the four CD8+ T cell subsets isolated from human PBMCs was analyzed using microarrays. DN cells were more similar to “early” highly differentiated cells, with decreased TNF and IFN‐γ production, impaired DNA damage response and apoptosis. Conversely, increased apoptosis and expression of cytokines, co‐inhibitory, and chemokine receptors were found in DP cells. Higher levels of DP CD8+ T cells were observed 7 days after Hepatitis B vaccination, and decreased levels of DP cells were found in rheumatoid arthritis patients. More DP and DN CD8+ T cells were present in the bone marrow, in comparison with PBMCs. In summary, our results indicate that DP and DN cells are distinct CD8+ T cell subsets displaying defined properties.

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<![CDATA[Nontuberculous Mycobacteria Show Differential Infectivity and Use Phospholipids to Antagonize LL-37]]> https://www.researchpad.co/article/Nd6e5934e-5183-4330-b763-05e69a9b236e

Comparisons of infectivity among the clinically important nontuberculous mycobacteria (NTM) species have not been explored in great depth. Rapid-growing mycobacteria, including Mycobacterium abscessus and M. porcinum, can cause indolent but progressive lung disease. Slow-growing members of the M. avium complex are the most common group of NTM to cause lung disease, and molecular approaches can now distinguish between several distinct species of M. avium complex including M. intracellulare, M. avium, M. marseillense, and M. chimaera. Differential infectivity among these NTM species may, in part, account for differences in clinical outcomes and response to treatment; thus, knowing the relative infectivity of particular isolates could increase prognostication accuracy and enhance personalized treatment. Using human macrophages, we investigated the infectivity and virulence of nine NTM species, as well as multiple isolates of the same species. We also assessed their capacity to evade killing by the antibacterial peptide cathelicidin (LL-37). We discovered that the ability of different NTM species to infect macrophages varied among the species and among isolates of the same species. Our biochemical assays implicate modified phospholipids, which may include a phosphatidylinositol or cardiolipin backbone, as candidate antagonists of LL-37 antibacterial activity. The high variation in infectivity and virulence of NTM strains suggests that more detailed microbiological and biochemical characterizations are necessary to increase our knowledge of NTM pathogenesis.

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<![CDATA[Early production of IL‐17A by γδ T cells in the trachea promotes viral clearance during influenza infection in mice]]> https://www.researchpad.co/article/N0f0e5896-5d07-436a-8796-807b3b260f3c

Abstract

The innate immune response generated against influenza infection is critical for the inhibition of viral dissemination. The trachea contains different types of innate immune cells that protect the respiratory tract from pathogen invasion. Among them, γδ T cells have the ability to rapidly generate large amounts of pro‐inflammatory cytokines to preserve mucosal barrier homeostasis during infection. However, little is known about their role during the early phase of influenza infection in the airways. In this study, we found that, early after infection, γδ T cells are recruited and activated in the trachea and outnumber αβ T cells during the course of the influenza infection that follows. We also showed that the majority of the recruited γδ T cells express the Vγ4 TCR chain and infiltrate in a process that involves the chemokine receptor CXCR3. In addition, we demonstrated that γδ T cells promote the recruitment of protective neutrophils and NK cells to the tracheal mucosa. Altogether, our results highlight the importance of the immune responses mediated by γδ T cells.

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