ciap-1 controls innate immunity to c. pneumoniae pulmonary infectionciap-1控制c .肺炎肺感染的先天免疫.pdfVIP

cIAP-1 Controls Innate Immunity to C. pneumoniae Pulmonary Infection 1 1 ¨ 2 4 3 3 Hridayesh Prakash , Daniel Becker , Linda Bohme , Lori Albert , Martin Witzenrath , Simone Rosseau , Thomas F. Meyer1, Thomas Rudel1,2* ´ ¨ 1 Department of Molecular Biology, Max Planck Institute for Infection Biology, Chariteplatz 1, Berlin, Germany, 2 Lehrstuhl fur Mikrobiologie Biozentrum, Am Hubland, ¨ ´ Wurzburg, Germany, 3 Department of Internal Medicine/Infectious Diseases, Charite, Humboldt University, Berlin, Germany, 4 The Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, Toronto, Ontario, Canada Abstract 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-c) was increased whereas that of Tumor Necrosis Factor (TNF-a) was reduced in