Chlamydophila pneumoniae induces production of the defensin-like MIG/CXCL9, which has in vitro antichlamydial activity.
CXC chemokines that lack the ELR motif, including the monokine induced by IFN-γ (MIG/CXCL9), the IFN-induced protein of 10 kDa (IP-10/CXCL10), and the IFN-inducible T-cell α-chemoattractant (I-TAC/CXCL11), have been shown to mediate the generation of type 1 immune responses and to possess defensin-like bactericidal effects. This study revealed that the infection of mice with Chlamydophila pneumoniae via the intranasal route resulted in the local expression of MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. The expression of IP-10/CXCL10 and I-TAC/CXCL11 mRNA peaked on day 4. On day 7, the expression of MIG/CXCL9 mRNA in the infected lungs was increased 156-fold relative to that in the uninfected mouse lungs. MIG/CXCL9 was also detected at a protein level from day 1, with the highest concentration in the supernatants of the infected lungs on day 7. The expression of IFN-γ displayed similar kinetics. C. pneumoniae and its inactivated form also induced the production of MIG/CXCL9 in mouse fibroblasts and in the murine macrophage cell line J774A in vitro. Cotreatment of the tissue cultures with C. pneumoniae and different quantities of IFN-γ resulted in strong increases in MIG/CXCL9 production. Recombinant MIG/CXCL9 exerted dose-dependent antibacterial activity against C. pneumoniae. Significant antichlamydial activity of MIG/CXCL9 was observed after a 15-min incubation period. Chlamydial proteins at a molecular weight of 60 kDa were identified by Far-Western blot assay and liquid chromatography-tandem mass spectrometry as binding molecules of MIG/CXCL9. The results of these experiments suggest that MIG/CXCL9 might play an important role in the innate and acquired defense mechanisms against C. pneumoniae.
Dept. of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary.
Emese P
EP
Balogh
Ildikó
I
Faludi
Dezso P
DP
Virók
Valéria
V
Endrész
Katalin
K
Burián
D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D026481:Blotting, Far-Western; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D054371:Chemokine CXCL11 / Q000096:biosynthesis; D054370:Chemokine CXCL9 / Q000096:biosynthesis*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D002853:Chromatography, Liquid; D023082:Defensins / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D011485:Protein Binding; D053719:Tandem Mass Spectrometry; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; C515203:Cxcl11 protein, mouse; C485969:Cxcl9 protein, mouse; D023082:Defensins; D007371:Interferon-gamma