T Cell-Independent Gamma Interferon and B Cells Cooperate To Prevent Mortality Associated with Disseminated Chlamydia muridarum Genital Tract Infection.
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ABSTRACT: CD4 T cells and antibody are required for optimal acquired immunity to Chlamydia muridarum genital tract infection, and T cell-mediated gamma interferon (IFN-?) production is necessary to clear infection in the absence of humoral immunity. However, the role of T cell-independent immune responses during primary infection remains unclear. We investigated this question by inoculating wild-type and immune-deficient mice with C. muridarum CM001, a clonal isolate capable of enhanced extragenital replication. Genital inoculation of wild-type mice resulted in transient dissemination to the lungs and spleen that then was rapidly cleared from these organs. However, CM001 genital infection proved lethal for STAT1-/- and IFNG-/- mice, in which IFN-? signaling was absent, and for Rag1-/- mice, which lacked T and B cells and in which innate IFN-? signaling was retained. In contrast, B cell-deficient muMT mice, which can generate a Th1 response, and T cell-deficient mice with intact B cell and innate IFN-? signaling survived. These data collectively indicate that IFN-? prevents lethal CM001 dissemination in the absence of T cells and suggests a B cell corequirement. Adoptive transfer of convalescent-phase immune serum but not naive IgM to Rag1-/- mice infected with CM001 significantly increased the survival time, while transfer of naive B cells completely rescued Rag1-/- mice from CM001 lethality. Protection was associated with a significant reduction in the lung chlamydial burden of genitally infected mice. These data reveal an important cooperation between T cell-independent B cell responses and innate IFN-? in chlamydial host defense and suggest that interactions between T cell-independent antibody and IFN-? are essential for limiting extragenital dissemination.
SUBMITTER: Poston TB
PROVIDER: S-EPMC6013674 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
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