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Vaccine driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

ABSTRACT: Subunit vaccine elicits lung tissue resident memmory CD4+ T-cells and confers lung protection against heterologous strain

ORGANISM(S): Mus musculus

PROVIDER: GSE174849 | GEO | 2021/08/31

REPOSITORIES: GEO

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Vaccine driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling [scRNA-Seq]

Project description:Subunit vaccine elicits lung tissue resident memmory CD4+ T-cells and confers lung protection against heterologous strain

2021-08-01 | GSE178385 | GEO

Subunit vaccine elicited lung TRM cells use fibroblast IL-17R signaling to provide serotype independent immunity against hypervirulent K. pneumoniae

Project description:Subunit vaccine conferred lung protection against heterologous strain through the augmentaion of lung tissue resident memmory CD4+ T-cells.

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Vaccine-driven lung TRM cells provide immunity against <i>Klebsiella</i> via fibroblast IL-17R signaling.

Project description:Tissue-resident memory (TRM) cells are thought to play a role in lung mucosal immunity to pathogens, but strategies to elicit TRM by mucosal vaccines have not yet been fully realized. Here, we formulated a vaccine composed of outer membrane protein (Omp) X from Klebsiella pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary route. This vaccine elicited both TH1 and TH17 cells that shared transcriptional features with cells elicited by heat-killed K. pneumoniae. Antibody responses were required to prevent bacterial dissemination but dispensable for lung-specific immunity. In contrast, lung immunity required CD4+ T cells, STAT3 expression, and IL-17R signaling in fibroblasts. Lung-specific CD4+ T cells from OmpX+LTA1–immunized mice were observed homing to the lung and could mediate protection against infection in an adoptive transfer model. Vaccine-elicited TH17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with TH1 cells, and TH17 cells conferred protection under conditions of transplant immunosuppression. These data demonstrate a promising vaccine strategy that elicits lung TRM cells and promotes serotype-independent immunity to K. pneumoniae.

| S-EPMC8796208 | biostudies-literature

Vaccine driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

Project description:Vaccine driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

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Vaccine driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling [scRNA-Seq]

Project description:Vaccine driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling [scRNA-Seq]

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Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections

Project description:MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Herein, we observe that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provided protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogated the protection conferred by MV130 against Influenza A virus respiratory infection. MV130 induced reprogramming of mouse bone marrow progenitor cells and human monocytes, promoting an enhanced cytokine production that relied on metabolic and epigenetic shifts. Our results unveil that the mucosal a dministration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity. This SuperSeries is composed of the SubSeries listed below.

2021-11-10 | GSE183721 | GEO

Subunit vaccine elicited lung TRM cells use fibroblast IL-17R signaling to provide serotype independent immunity against hypervirulent K. pneumoniae

Project description:Subunit vaccine elicited lung TRM cells use fibroblast IL-17R signaling to provide serotype independent immunity against hypervirulent K. pneumoniae

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Cytomegalovirus vaccine vector-induced effector memory CD4+ T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza

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BCG induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-y mediated trained immunity

Project description:After a century of the Bacillus Calmette-Guérin (BCG) vaccine, our understanding of its protection against homologous (Mycobacterium tuberculosis) or heterologous (e.g. influenza virus) infections is still limited. Here we show that systemic (intravenous) BCG vaccination (BCG-iv) provides significant protection against subsequent influenza A virus (IAV) infection in mice. We further demonstrate that the BCG-mediated cross-protection against IAV is largely due to the enrichment of conventional CD4+ αβ effector memory T cells that express high levels of CX3CR1hi in circulation trafficking into the lung parenchyma. Importantly, pulmonary CX3CR1hi T cells limit early viral infection in an antigen-independent manner via potent IFNγ production, which subsequently enhances long-term antimicrobial activity of the innate immune system like alveolar macrophages. Similarly, we uncover a prominent IFNγ signature in which its increased basal production was associated with enhanced BCG-mediated heterologous innate memory responses in BCG-vaccinated humans. These results offer insight into the unknown mechanism by which BCG has persistently displayed broad protection against non-tuberculous infections via a crosstalk between adaptive and innate memory responses.

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