title: Role of proapoptotic BAX in propagation of Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) and the host inflammatory response.
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.
authors.affiliation: Université Paris 7, Institut Pasteur, Unité de Biologie Moléculaire du Gène, INSERM U277, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Perfettini
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.forename: Charles W
authors.initials: CW
authors.lastname: Andrews
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Korsmeyer
authors.forename: Roger G
authors.initials: RG
authors.lastname: Rank
authors.forename: Toni
authors.initials: T
authors.lastname: Darville
mesh_terms: D000818:Animals; D017209:Apoptosis; D002690:Chlamydia Infections / Q000473:pathology; D023502:Chlamydia muridarum / Q000378:metabolism*; D005260:Female; D006099:Granuloma / Q000378:metabolism; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D013997:Time Factors; D051028:bcl-2-Associated X Protein
chemical_list: C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein