Hypoxia abrogates antichlamydial properties of IFN-γ in human fallopian tube cells in vitro and ex vivo.
IFN-γ has an important role in the adaptive immune response against intracellular pathogens. In urogenital tract (UGT) infections with the obligate intracellular pathogen Chlamydia trachomatis, IFN-γ-mediated control of chlamydial growth implies the JAK-STAT signaling cascades and subsequent induction of the indoleamine 2,3-dioxygenase (IDO). As oxygen concentrations in the UGT are low under physiological conditions (O(2) < 5%) and further decrease during an inflammatory process, we wondered whether antibacterial properties of IFN-γ are maintained under hypoxic conditions. Using primary cells that were isolated from human fallopian tubes and an ex vivo human fallopian tube model (HFTM), we found that even high IFN-γ concentrations (200 units/mL) were not sufficient to limit growth of C. trachomatis under hypoxia. Reduced antibacterial activity of IFN-γ under hypoxia was restricted to the urogenital serovars D and L(2), but was not observed with the ocular serovar A. Impaired effectiveness of IFN-γ on chlamydial growth under hypoxia was accompanied by reduced phosphorylation of Stat-1 on Tyr701 and diminished IDO activity. This study shows that IFN-γ effector functions on intracellular C. trachomatis depend on the environmental oxygen supply, which could explain inadequate bacterial clearance and subsequent chronic infections eventually occurring in the UGT of women.
Institute of Medical Microbiology and Hygiene, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany.
Anna
A
Roth
Peter
P
König
Ger
G
van Zandbergen
Matthias
M
Klinger
Thomas
T
Hellwig-Bürgel
Walter
W
Däubener
Michael K
MK
Bohlmann
Jan
J
Rupp
D056704:Adaptive Immunity; D002690:Chlamydia Infections / Q000209:etiology / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000254:growth & development / Q000276:immunology; D005187:Fallopian Tubes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000276:immunology / Q000382:microbiology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology*; D014552:Urinary Tract Infections / Q000209:etiology / Q000276:immunology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma