cIAP-1 controls innate immunity to C. pneumoniae pulmonary infection.
The resistance of epithelial cells infected with Chlamydophila pneumoniae for apoptosis has been attributed to the induced expression and increased stability of anti-apoptotic proteins called inhibitor of apoptosis proteins (IAPs). The significance of cellular inhibitor of apoptosis protein-1 (cIAP-1) in C. pneumoniae pulmonary infection and innate immune response was investigated in cIAP-1 knockout (KO) mice using a novel non-invasive intra-tracheal infection method. In contrast to wildtype, cIAP-1 knockout mice failed to clear the infection from their lungs. Wildtype mice responded to infection with a strong inflammatory response in the lung. In contrast, the recruitment of macrophages was reduced in cIAP-1 KO mice compared to wildtype mice. The concentration of Interferon gamma (IFN-gamma) was increased whereas that of Tumor Necrosis Factor (TNF-alpha) was reduced in the lungs of infected cIAP-1 KO mice compared to infected wildtype mice. Ex vivo experiments on mouse peritoneal macrophages and splenocytes revealed that cIAP-1 is required for innate immune responses of these cells. Our findings thus suggest a new immunoregulatory role of cIAP-1 in the course of bacterial infection.
Prakash
Hridayesh
H
Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, Berlin, Germany.
Becker
Daniel
D
Böhme
Linda
L
Albert
Lori
L
Witzenrath
Martin
M
Rosseau
Simone
S
Meyer
Thomas F
TF
Rudel
Thomas
T
D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000302:isolation & purification; D007113:Immunity, Innate / Q000502:physiology*; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051034:Inhibitor of Apoptosis Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma