title: MyD88 is pivotal for the early inflammatory response and subsequent bacterial clearance and survival in a mouse model of Chlamydia pneumoniae pneumonia.
abstract: Chlamydia pneumoniae is the causative agent of respiratory tract infections and a number of chronic diseases. Here we investigated the involvement of the common TLR adaptor molecule MyD88 in host responses to C. pneumoniae-induced pneumonia in mice. MyD88-deficient mice were severely impaired in their ability to mount an acute early inflammatory response toward C. pneumoniae. Although the bacterial burden in the lungs was comparable 5 days after infection, MyD88-deficient mice exhibited only minor signs of pneumonia and reduced expression of inflammatory mediators. MyD88-deficient mice were unable to up-regulate proinflammatory cytokines and chemokines, demonstrated delayed recruitment of CD8+ and CD4+ T cells to the lungs, and were unable to clear the pathogen from their lungs at day 14. At day 14 the MyD88-deficent mice developed a severe, chronic lung inflammation with elevated IL-1beta and IFN-gamma leading to increased mortality, whereas wild-type mice as well as TLR2- or TLR4-deficient mice recovered from acute pneumonia and did not show delayed bacterial clearance. Thus, MyD88 is essential to recognize C. pneumoniae infection and initiate a prompt and effective immune host response against this organism leading to clearance of bacteria from infected lungs.
authors.affiliation: Division of Pediatrics Infectious Diseases and Immunology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90048, USA.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Naiki
authors.forename: Kathrin S
authors.initials: KS
authors.lastname: Michelsen
authors.forename: Nicolas W J
authors.initials: NW
authors.lastname: Schröder
authors.forename: Randa
authors.initials: R
authors.lastname: Alsabeh
authors.forename: Anatoly
authors.initials: A
authors.lastname: Slepenkin
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.forename: Yonca
authors.initials: Y
authors.lastname: Bulut
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Wong
authors.forename: Ellena M
authors.initials: EM
authors.lastname: Peterson
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D001835:Body Weight; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D023521:Chlamydophila Infections / Q000382:microbiology*; D016993:Chlamydophila pneumoniae / Q000378:metabolism* / Q000472:pathogenicity*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4