Tumor necrosis factor alpha production from CD8+ T cells mediates oviduct pathological sequelae following primary genital Chlamydia muridarum infection.

Abstract

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-α) production (TNF-α(-/-) 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-α 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-α(-/-), CD8(+) T cells at the time of challenge restored hydrosalpinx to levels observed in wild-type C57BL/6 mice, suggesting that TNF-α production from CD8(+) T cells is important for pathogenesis. Additionally, repletion of TNF-α(-/-) mice with TNF-α(+/+) CD8(+) T cells significantly enhanced the incidence of hydrosalpinx and oviduct dilatation compared to those of TNF-α(-/-) mice but not to the levels found in wild-type mice, suggesting that TNF-α 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-α production to Chlamydia-induced reproductive tract sequelae.

• Authors: Ashlesh K Murthy, Weidang Li, Bharat K R Chaganty, Sangamithra Kamalakaran, M Neal Guentzel, J Seshu, Thomas G Forsthuber, Guangming Zhong, Bernard P Arulanandam
• Journal: Infection and immunity (Infect Immun) Vol. 79 Issue 7 Pg. 2928-35 (Jul 2011) ISSN: 1098-5522 [Electronic] United States
• PMID: 21536799 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Necrosis Factor-alpha
• Perforin

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Chlamydia Infections (immunology, microbiology, pathology)
• Chlamydia muridarum
• Fallopian Tubes (microbiology, pathology)
• Female
• Genital Diseases, Female (immunology, microbiology, pathology)
• HeLa Cells
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Perforin (biosynthesis, genetics)
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Vagina (microbiology)