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Contribution of STAT1 to innate and adaptive immunity during type I interferon-mediated lethal virus infection.

ABSTRACT: Signal transducers and activators of transcription (STAT) 1 is critical for cellular responses to type I interferons (IFN-Is), with the capacity to determine the outcome of viral infection. We previously showed that while wildtype (WT) mice develop mild disease and survive infection with lymphocytic choriomeningitis virus (LCMV), LCMV infection of STAT1-deficient mice results in a lethal wasting disease that is dependent on IFN-I and CD4+ cells. IFN-Is are considered to act as a bridge between innate and adaptive immunity. Here, we determined the relative contribution of STAT1 on innate and adaptive immunity during LCMV infection. We show that STAT1 deficiency results in a biphasic disease following LCMV infection. The initial, innate immunity-driven phase of disease was characterized by rapid weight loss, thrombocytopenia, systemic cytokine and chemokine responses and leukocyte infiltration of infected organs. In the absence of an adaptive immune response, this first phase of disease largely resolved resulting in survival of the infected host. However, in the presence of adaptive immunity, the disease progressed into a second phase with continued cytokine and chemokine production, persistent leukocyte extravasation into infected tissues and ultimately, host death. Overall, our findings demonstrate the key contribution of STAT1 in modulating innate and adaptive immunity during type I interferon-mediated lethal virus infection.

SUBMITTER: Jung SR

PROVIDER: S-EPMC7192509 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Contribution of STAT1 to innate and adaptive immunity during type I interferon-mediated lethal virus infection.

Jung So Ri SR Ashhurst Thomas M TM West Phillip K PK Viengkhou Barney B King Nicholas J C NJC Campbell Iain L IL Hofer Markus J MJ

PLoS pathogens 20200420 4

Signal transducers and activators of transcription (STAT) 1 is critical for cellular responses to type I interferons (IFN-Is), with the capacity to determine the outcome of viral infection. We previously showed that while wildtype (WT) mice develop mild disease and survive infection with lymphocytic choriomeningitis virus (LCMV), LCMV infection of STAT1-deficient mice results in a lethal wasting disease that is dependent on IFN-I and CD4+ cells. IFN-Is are considered to act as a bridge between i ...[more]

PMID: 32310998

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Dataset Information

Contribution of STAT1 to innate and adaptive immunity during type I interferon-mediated lethal virus infection.

Publications

Contribution of STAT1 to innate and adaptive immunity during type I interferon-mediated lethal virus infection.

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