Host immune responses after hypoxic reactivation of IFN-γ induced persistent Chlamydia trachomatis infection.
Genital tract infections with Chlamydia trachomatis (C. trachomatis) are the most frequent sexually transmitted disease worldwide. Severe clinical sequelae such as pelvic inflammatory disease (PID), tubal occlusion, and tubal infertility are linked to inflammatory processes of chronically infected tissues. The oxygen concentrations in the female urogenital tract are physiologically low and further diminished (0.5-5% O2, hypoxia) during an ongoing inflammation. However, little is known about the effect of a low oxygen environment on genital C. trachomatis infections. In this study, we investigated the host immune responses during reactivation of IFN-γ induced persistent C. trachomatis infection under hypoxia. For this purpose, the activation of the MAP-kinases p44/42 and p38 as well as the induction of the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MCP-1 were analyzed. Upon hypoxic reactivation of IFN-γ induced persistent C. trachomatis infection, the phosphorylation of the p44/42 but not of the p38 MAP-kinase was significantly diminished compared to IFN-γ induced chlamydial persistence under normoxic condition. In addition, significantly reduced IL-6 and IL-8 mRNA expression levels were observed for reactivated Chlamydiae under hypoxia compared to a persistent chlamydial infection under normoxia. Our findings indicate that hypoxia not only reactivates IFN-γ induced persistent C. trachomatis infections resulting in increased bacterial growth and progeny but also dampens inflammatory host immune signaling responses that are normally observed in a normoxic environment.
Institute of Medical Microbiology and Hygiene, University of Lübeck Lübeck, Germany.
Stefan
S
Jerchel
Institute of Medical Microbiology and Hygiene, University of Lübeck Lübeck, Germany.
Inga
I
Kaufhold
Institute of Medical Microbiology and Hygiene, University of Lübeck Lübeck, Germany.
Larissa
L
Schuchardt
Institute of Medical Microbiology and Hygiene, University of Lübeck Lübeck, Germany.
Kensuke
K
Shima
Institute of Medical Microbiology and Hygiene, University of Lübeck Lübeck, Germany ; Medical Clinic III/Infectious Diseases, University Hospital of Schleswig-Holstein Lübeck, Germany.
Jan
J
Rupp
D015687:Cell Hypoxia; D002460:Cell Line; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D007371:Interferon-gamma; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
Chlamydia trachomatis; hypoxia; immune response; persistence; reactivation