First Author | Murthy AK | Year | 2011 |
Journal | Infect Immun | Volume | 79 |
Issue | 7 | Pages | 2928-35 |
PubMed ID | 21536799 | Mgi Jnum | J:173482 |
Mgi Id | MGI:5014136 | Doi | 10.1128/IAI.05022-11 |
Citation | Murthy AK, et al. (2011) Tumor Necrosis Factor Alpha Production from CD8+ T Cells Mediates Oviduct Pathological Sequelae following Primary Genital Chlamydia muridarum Infection. Infect Immun 79(7):2928-35 |
abstractText | The immunopathogenesis of Chlamydia trachomatis-induced oviduct pathological sequelae is not well understood. Mice genetically deficient in perforin (perforin(-/-) mice) or tumor necrosis factor alpha (TNF-alpha) production (TNF-alpha(-/-) mice) displayed comparable vaginal chlamydial clearance rates but significantly reduced oviduct pathology (hydrosalpinx) compared to that of wild-type mice. Since both perforin and TNF-alpha are effector mechanisms of CD8(+) T cells, we evaluated the role of CD8(+) T cells during genital Chlamydia muridarum infection and oviduct sequelae. Following vaginal chlamydial challenge, (i) mice deficient in TAP I (and therefore the major histocompatibility complex [MHC] I pathway and CD8(+) T cells), (ii) wild-type mice depleted of CD8(+) T cells, and (iii) mice genetically deficient in CD8 (CD8(-/-) mice) all displayed similar levels of vaginal chlamydial clearance but significantly reduced hydrosalpinx, compared to those of wild-type C57BL/6 mice, suggesting a role for CD8(+) T cells in chlamydial pathogenesis. Repletion of CD8(-/-) mice with wild-type or perforin(-/-), but not TNF-alpha(-/-), CD8(+) T cells at the time of challenge restored hydrosalpinx to levels observed in wild-type C57BL/6 mice, suggesting that TNF-alpha production from CD8(+) T cells is important for pathogenesis. Additionally, repletion of TNF-alpha(-/-) mice with TNF-alpha(+/+) CD8(+) T cells significantly enhanced the incidence of hydrosalpinx and oviduct dilatation compared to those of TNF-alpha(-/-) mice but not to the levels found in wild-type mice, suggesting that TNF-alpha production from CD8(+) T cells and non-CD8(+) cells cooperates to induce optimal oviduct pathology following genital chlamydial infection. These results provide compelling new evidence supporting the contribution of CD8(+) T cells and TNF-alpha production to Chlamydia-induced reproductive tract sequelae. |