Silencing or permanent activation: host-cell responses in models of persistent Chlamydia pneumoniae infection.
Chlamydia pneumoniae causes respiratory infections. In chronic diseases associated with Chlamydia, such as arteriosclerosis, C. pneumoniae is present in a persistent form, which might participate in pathogenesis of chronic inflammatory disease. To elucidate how these intracellular bacteria modulate host-cells during persistence, we compared the expression pattern of a range of host genes after short (24 h) and long (up to 7 days) times of chlamydia infection in HeLa-cells. One day post infection, in three cell-culture models of persistence, namely treatment with penicillin or IFN-gamma, or iron-depletion, infection induced the genes of CTGF, IL-6, IL-8, IL-11, LIF, EGR-1 and ETV4 in a similar fashion. However, after a longer time, two modes of host-cell reaction emerged that were dependent on the persistence model used. After IFN-gamma and penicillin treatment chlamydia-induced host-cell gene expression was inhibited, while it stayed upregulated in iron-depletion. Human monocytes/macrophages, in which persistence naturally occurs, were additionally investigated: for several genes, UV-inactivated and viable chlamydia caused long-lasting upregulation. Thus, this study reveals (i) the ability of C. pneumoniae to participate in two putative pathomechanisms of persistence, silencing and permanent activation, which might represent different in vivo situations and (ii) a strong dependence on the mode of persistence induction.
Peters
Jan
J
Department of Medical Microbiology, Medical School Hannover, D-30623 Hannover, Germany.
Hess
Simone
S
Endlich
Katja
K
Thalmann
Jessica
J
Holzberg
David
D
Kracht
Michael
M
Schaefer
Myriam
M
Bartling
Gerda
G
Klos
Andreas
A
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000235:genetics; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000502:physiology*; D055513:Connective Tissue Growth Factor; D003470:Culture Media; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism; D000090463:Iron Deficiencies; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D010400:Penicillin G / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D015854:Up-Regulation
D017500:Adenovirus E1A Proteins; C526317:CCN2 protein, human; D003470:Culture Media; C079853:ETV4 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D007371:Interferon-gamma; D010400:Penicillin G