T-independent IFNγ and B cells synergize to prevent mortality associated with disseminated Chlamydia muridarum genital infection
| Autor: | Taylor Poston, Catherine O’Connell, Jenna Girardi, Jeanne E. Sullivan, Uma Nagarajan, Anthony Marinov, Amy Scurlock, Toni Darville |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 200:117.6-117.6 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.200.supp.117.6 |
| Popis: | CD4 T cells and antibody are required for optimal acquired immunity to C. muridarum genital tract infection, and T cell-mediated IFNγ production is necessary to clear infection in the absence of humoral immunity. However, the role of protective T cell-independent immune responses against primary infection remain unclear. We addressed this problem by inoculating wild-type and immune-deficient mice with a plaque-purified strain (CM001) isolated from C. muridarum Nigg stock capable of enhanced extragenital replication. Genital CM001 inoculation resulted in transient dissemination to the lungs and spleen in wild-type mice prior to clearance. However, CM001 genital infection induced lethality in STAT1−/− and IFNG−/− mice, where IFNγ signaling is absent, and in Rag1−/− mice that lack T and B cells but are competent for innate IFNγ signaling. In contrast, muMT, nude, and Tcra−/− mice survived. These data collectively indicate that IFNγ prevents lethal CM001 infection in the absence of T cells and suggest a B cell co-requirement for protection. Adoptive transfer of convalescent immune sera, but not naïve IgM antibody, to Rag1−/− mice significantly increased survival time and transfer of naïve B cells completely rescued Rag1−/− mice against CM001 lethality. Protection was associated with a significant reduction in the lung chlamydial burden of genitally infected mice. These data reveal an important synergism between T-independent B cell responses and innate IFNγ in chlamydial host defense, and suggest cooperative interactions between T-independent IgG and IFNγ are essential for limiting extragenital dissemination. |
| Databáze: | OpenAIRE |
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