Inhibition of apoptosis by gamma interferon in cells and mice infected with Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis).
The effect of gamma interferon (IFN-gamma) on apoptosis due to infection by Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) was studied in epithelial cells in culture and in the genital tracts of mice. IFN-gamma concentrations that induce the formation of aberrant, persistent chlamydiae inhibit apoptosis due to C. muridarum infection. In cells treated with an IFN-gamma concentration that leads to the development of a heterogenous population of normal and aberrant Chlamydia vacuoles, apoptosis was inhibited preferentially in cells that contained the aberrant vacuoles. The inhibitory effect of IFN-gamma appears to be due in part to expression of host cell indoleamine 2,3-dioxygenase activity, since inhibition of apoptosis could be partially reversed through coincubation with exogenous tryptophan. Apoptotic cells were observed in the genital tracts of wild-type mice infected with C. muridarum, and a significantly larger number of apoptotic cells was detected in infected IFN-gamma-deficient mice. These results suggest that IFN-gamma may contribute to pathogenesis of persistent Chlamydia infections in vivo by preventing apoptosis of infected cells.
Perfettini
Jean-Luc
JL
Unité de Biologie Moléculaire du Gène, INSERM U277, Université Paris 7, 75724 Paris Cedex 15, France.
Darville
Toni
T
Dautry-Varsat
Alice
A
Rank
Roger G
RG
Ojcius
David M
DM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002690:Chlamydia Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D002692:Chlamydia trachomatis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D014364:Tryptophan / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000096:biosynthesis; D014621:Vagina / Q000473:pathology
D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase