Role of proapoptotic BAX in propagation of Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) and the host inflammatory response

Jean Luc Perfettini, David M. Ojcius*, Charles W. Andrews, Stanley J. Korsmeyer, Roger G. Rank, Toni Darville

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

47 Scopus citations

Abstract

The BCL-2 family member BAX plays a critical role in regulating apoptosis. Surprisingly, bax-deficient mice display limited phenotypic abnormalities. Here we investigate the effect of BAX on infection by the sexually transmitted pathogen, Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis). Bax-/- cells are relatively resistant to Chlamydia-induced apoptosis, and fewer bacteria are recovered after two infection cycles from Bax-/- cells than from wild-type cells. These results suggest that BAX-dependent apoptosis may be used to initiate a new round of infection, most likely by releasing Chlamydia-containing apoptotic bodies from infected cells that could be internalized by neighboring uninfected cells. Nonetheless, infected Bax-/- cells die through necrosis, which is normally associated with inflammation, more often than infected wild-type cells. These studies were confirmed in mice infected intravaginally with C. muridarum; since the infection disappears more quickly from Bax-/- mice than from wild-type mice, secretion of proinflammatory cytokines is increased in Bax-/- mice, and large granulomas are present in the genital tract of Bax-/- mice. Taken together, these data suggest that chlamydia-induced apoptosis via BAX contributes to bacterial propagation and decreases inflammation. Bax deficiency results in lower infection and an increased inflammatory cytokine response associated with more severe pathology.

Original languageEnglish
Pages (from-to)9496-9502
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number11
DOIs
StatePublished - 14 03 2003
Externally publishedYes

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