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

Ashlesh K. Murthy, Weidang Li, Bharat K.R. Chaganty, Sangamithra Kamalakaran, M. Neal Guentzel, J. Seshu, Thomas G. Forsthuber, Guangming Zhong, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

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 Chlamydiainduced reproductive tract sequelae.

Original languageEnglish (US)
Pages (from-to)2928-2935
Number of pages8
JournalInfection and immunity
Volume79
Issue number7
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Infectious Diseases
  • Parasitology
  • Microbiology
  • Immunology

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