scholarly journals Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus–infected mice

2009 ◽  
Vol 206 (11) ◽  
pp. 2339-2349 ◽  
Author(s):  
Corine H. GeurtsvanKessel ◽  
Monique A.M. Willart ◽  
Ingrid M. Bergen ◽  
Leonie S. van Rijt ◽  
Femke Muskens ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Plasma Cells ◽  
Influenza Virus Infection ◽  
Infectious Agents ◽  
Virus Clearance ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Tertiary lymphoid organs (TLOs) are organized aggregates of B and T cells formed in postembryonic life in response to chronic immune responses to infectious agents or self-antigens. Although CD11c+ dendritic cells (DCs) are consistently found in regions of TLO, their contribution to TLO organization has not been studied in detail. We found that CD11chi DCs are essential for the maintenance of inducible bronchus-associated lymphoid tissue (iBALT), a form of TLO induced in the lungs after influenza virus infection. Elimination of DCs after the virus had been cleared from the lung resulted in iBALT disintegration and reduction in germinal center (GC) reactions, which led to significantly reduced numbers of class-switched plasma cells in the lung and bone marrow and reduction in protective antiviral serum immunoglobulins. Mechanistically, DCs isolated from the lungs of mice with iBALT no longer presented viral antigens to T cells but were a source of lymphotoxin (LT) β and homeostatic chemokines (CXCL-12 and -13 and CCL-19 and -21) known to contribute to TLO organization. Like depletion of DCs, blockade of LTβ receptor signaling after virus clearance led to disintegration of iBALT and GC reactions. Together, our data reveal a previously unappreciated function of lung DCs in iBALT homeostasis and humoral immunity to influenza virus.

scholarly journals Dendritic Cells Targeting Lactobacillus plantarum Strain NC8 with a Surface-Displayed Single-Chain Variable Fragment of CD11c Induce an Antigen-Specific Protective Cellular Immune Response

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Jing Liu ◽  
Guilian Yang ◽  
Haibin Huang ◽  
Chunwei Shi ◽  
Xing Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Lactobacillus Plantarum ◽  
Influenza Virus Infection ◽  
Cell Culture Supernatant ◽  
Single Chain ◽  
Ifn Γ

ABSTRACT Influenza A virus (H1N1) is an acute, highly contagious respiratory virus. The use of lactic acid bacteria (LAB) to deliver mucosal vaccines against influenza virus infection is a research hot spot. In this study, two recombinant Lactobacillus plantarum strains expressing hemagglutinin (HA) alone or coexpressing aCD11c-HA to target HA protein to dendritic cells (DCs) by fusion to an anti-CD11c single-chain antibody (aCD11c) were constructed. The activation of bone marrow dendritic cells (BMDCs) by recombinant strains and the interaction of activated BMDCs and sorted CD4+ or CD8+ T cells were evaluated through flow cytometry in vitro, and cellular supernatants were assessed by using an enzyme-linked immunosorbent assay kit. The results demonstrated that, compared to the HA strain, the aCD11c-HA strain significantly increased the activation of BMDCs and increased the production of CD4+ gamma interferon-positive (IFN-γ+) T cells, CD8+ IFN-γ+ T cells, and IFN-γ in the cell culture supernatant in vitro. Consistent with these results, the aCD11c-HA strain clearly increased the activation and maturation of DCs, the HA-specific responses of CD4+ IFN-γ+ T cells, CD8+ IFN-γ+ T cells, and CD8+ CD107a+ T cells, and the proliferation of T cells in the spleen, finally increasing the levels of specific antibodies and neutralizing antibodies in mice. In addition, the protection of immunized mice was observed after viral infection, as evidenced by improved weight loss, survival, and lung pathology. The adoptive transfer of CD8+ T cells from the aCD11c-HA mice to NOD/Lt-SCID mice resulted in a certain level of protection after influenza virus infection, highlighting the efficacy of the aCD11c targeting strategy.

scholarly journals Effect of Vitamin A Deficiency in Dysregulating Immune Responses to Influenza Virus and Increasing Mortality Rates After Bacterial Coinfections

2020 ◽  
Author(s):  
Rhiannon R Penkert ◽  
Amanda P Smith ◽  
Eike R Hrincius ◽  
Jonathan A McCullers ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Vitamin A ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Bacterial Infections ◽  
Vitamin A Deficiency ◽  
Influenza Virus Infection ◽  
Viral Clearance ◽  
Lymphoid Structures

Abstract Background Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbid conditions associated with influenza. Because vitamin A deficiency (VAD) and insufficiency are frequent in both developed and developing countries, we asked how VAD influences coinfection severity. Methods VAD and control mice were infected with influenza virus for evaluation of inflammatory cytokines, cellular immune responses, and viral clearance. Influenza-infected mice were coinfected with Streptococcus pneumoniae to study weight loss and survival. Results Naive VAD mouse lungs exhibited dysregulated immune function. Neutrophils were enhanced in frequency and there was a significant reduction in RANTES (regulated on activation of normal T cells expressed and secreted), a chemokine instrumental in T-cell homing and recruitment. After influenza virus infection, VAD mice experienced failures in CD4+ T-cell recruitment and B-cell organization into lymphoid structures in the lung. VAD mice exhibited higher viral titers than controls and slow viral clearance. There were elevated levels of inflammatory cytokines and innate cell subsets in the lungs. However, arginase, a marker of alternatively activated M2 macrophages, was rare. When influenza-infected VAD animals were exposed to bacteria, they experienced a 100% mortality rate. Conclusion Data showed that VAD dysregulated the immune response. Consequently, secondary bacterial infections were 100% lethal in influenza-infected VAD mice.

scholarly journals Chronic Heat Stress Inhibits Immune Responses to H5N1 Vaccination through Regulating CD4+CD25+Foxp3+Tregs

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Di Meng ◽  
Yanxin Hu ◽  
Chong Xiao ◽  
Tangting Wei ◽  
Qiang Zou ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Heat Stress ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Influenza Virus Infection ◽  
H5n1 Influenza ◽  
Avian Influenza Virus H5n1 ◽  
Pathogenic Avian Influenza Virus ◽  
Negative Impacts

Chronic heat stress (CHS) is known to have negative impacts on the immune responses in animals and increases their susceptibility to infections including the highly pathogenic avian influenza virus H5N1. However, the role of regulatory T cells (Tregs) in CHS immunosuppression remains largely undefined. In this study, we demonstrated a novel mechanism by which CHS suppressed both Th1 and Th2 immune responses and dramatically decreased the protective efficacy of the formalin-inactivated H5N1 vaccine against H5N1 influenza virus infection. This suppression was found to be associated with the induced generation of CD4+CD25+FoxP3+Tregs and the increased secretions of IL-10 and TGF-βin CD4+T cells. Adoptive transfer of the induced Tregs also suppressed the protective efficacy of formalin-inactivated H5N1 virus immunization. Collectively, this study identifies a novel mechanism of CHS immunosuppression mediated by regulating CD4+CD25+Foxp3+Tregs.

scholarly journals IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection

2010 ◽  
Vol 207 (3) ◽  
pp. 521-534 ◽  
Author(s):  
Jodi McGill ◽  
Nico Van Rooijen ◽  
Kevin L. Legge
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Cell Survival ◽  
Cd8 T Cells ◽  
Influenza Virus Infection ◽  
Cd8 T Cell ◽  
T Cell Survival

We have recently demonstrated that peripheral CD8 T cells require two separate activation hits to accumulate to high numbers in the lungs after influenza virus infection: a primary interaction with mature, antigen-bearing dendritic cells (DCs) in the lymph node, and a second, previously unrecognized interaction with MHC I–viral antigen–bearing pulmonary DCs in the lungs. We demonstrate that in the absence of lung-resident DC subsets, virus-specific CD8 T cells undergo significantly increased levels of apoptosis in the lungs; however, reconstitution with pulmonary plasmacytoid DCs and CD8α+ DCs promotes increased T cell survival and accumulation in the lungs. Further, our results show that the absence of DCs after influenza virus infection results in significantly reduced levels of IL-15 in the lungs and that pulmonary DC–mediated rescue of virus-specific CD8 T cell responses in the lungs requires trans-presentation of IL-15 via DC-expressed IL-15Rα. This study demonstrates a key, novel requirement for DC trans-presented IL-15 in promoting effector CD8 T cell survival in the respiratory tract after virus infection, and suggests that this trans-presentation could be an important target for the development of unique antiviral therapies and more effective vaccine strategies.

scholarly journals TGF-β induced CXCL13 in CD8+ T cells is associated with tertiary lymphoid structures in cancer

2018 ◽  
Author(s):  
HH Workel ◽  
JM Lubbers ◽  
R Arnold ◽  
T Prins ◽  
P van der Vlies ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Tumors ◽  
Unexpected Finding ◽  
Follicular Helper ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

AbstractCoordinated immune responses against human tumors are frequently characterized by tertiary lymphoid structures (TLS) which predict improved prognosis. The development of TLS is dependent on the chemokine CXCL13, reported to be secreted by dendritic cells and follicular helper T cells only. We report the unexpected finding that CXCL13 is also secreted by activated CD8+ T cells following stimulation by transforming growth factor beta (TGF-β). Using single cell RNA sequencing we found that expression ofCXCL13in CD8+ T cells was restricted to the intraepithelial CD103+ population. Accordingly, CD8+ T cells activated in the presence of TGF-β simultaneously upregulated CD103 and secreted CXCL13.CXCL13expression was strongly correlated with neo-antigen burden and cytolytic gene signatures in bulk tumors. In line with this, TLS were abundant in neo-antigen-high, CD103+ T cell-enriched tumors. TGF-β thus appears to play a role in coordinating immune responses against human tumors through CD8-dependent CXCL13-associated formation of TLS.

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