title: CD4+ T cell expression of MyD88 is essential for normal resolution of Chlamydia muridarum genital tract infection.
abstract: Resolution of Chlamydia genital tract infection is delayed in the absence of MyD88. In these studies, we first used bone marrow chimeras to demonstrate a requirement for MyD88 expression by hematopoietic cells in the presence of a wild-type epithelium. Using mixed bone marrow chimeras we then determined that MyD88 expression was specifically required in the adaptive immune compartment. Furthermore, adoptive transfer experiments revealed that CD4(+) T cell expression of MyD88 was necessary for normal resolution of genital tract infection. This requirement was associated with a reduced ability of MyD88(-/-)CD4(+) T cells to accumulate in the draining lymph nodes and genital tract when exposed to the same inflammatory milieu as wild-type CD4(+) T cells. We also demonstrated that the impaired infection control we observed in the absence of MyD88 could not be recapitulated by deficiencies in TLR or IL-1R signaling. In vitro, we detected an increased frequency of apoptotic MyD88(-/-)CD4(+) T cells upon activation in the absence of exogenous ligands for receptors upstream of MyD88. These data reveal an intrinsic requirement for MyD88 in CD4(+) T cells during Chlamydia infection and indicate that the importance of MyD88 extends beyond innate immune responses by directly influencing adaptive immunity.
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201;
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Frazer
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Sullivan
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Zurenski
authors.forename: Margaret
authors.initials: M
authors.lastname: Mintus
authors.forename: Tammy E
authors.initials: TE
authors.lastname: Tomasak
authors.forename: Daniel
authors.initials: D
authors.lastname: Prantner
authors.forename: Uma M
authors.initials: UM
authors.lastname: Nagarajan
authors.forename: Toni
authors.initials: T
authors.lastname: Darville
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D005836:Genitalia, Female / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D060737:Reproductive Tract Infections / Q000276:immunology* / Q000382:microbiology
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1
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