Document Detail


Role of MyD88 and Toll-like receptors 2 and 4 in the sensing of Parachlamydia acanthamoebae.
MedLine Citation:
PMID:  20837714     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Parachlamydia acanthamoebae is a Chlamydia-related organism whose pathogenic role in pneumonia is supported by serological and molecular clinical studies and an experimental mouse model of lung infection. Toll-like receptors (TLRs) play a seminal role in sensing microbial products and initiating innate immune responses. The aim of this study was to investigate the roles of MyD88, TLR2, and TLR4 in the interaction of Parachlamydia with macrophages. Here, we showed that Parachlamydia entered bone-marrow derived macrophages (BMDMs) in a TLR-independent manner but did not multiply intracellularly. Interestingly, compared to live bacteria, heat-inactivated Parachlamydia induced the production of substantial amounts of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), and IL-12p40 by BMDMs and of TNF and IL-6 by peritoneal macrophages as well as RAW 264.7 and J774 macrophage cell lines. Cytokine production by BMDMs, which was partially inhibited upon trypsin treatment of Parachlamydia, was dependent on MyD88, TLR4, and, to a lesser extent, TLR2. Finally, MyD88(-/-), TLR4(-/-), and TLR2(-/-) mice were as resistant as wild-type mice to lung infection following the intratracheal instillation of Parachlamydia. Thus, in contrast to Chlamydia pneumoniae, Parachlamydia acanthamoebae weakly stimulates macrophages, potentially compensating for its low replication capacity in macrophages by escaping the innate immune surveillance.
Authors:
Thierry Roger; Nicola Casson; Antony Croxatto; José Manuel Entenza; Marc Pusztaszeri; Shizuo Akira; Marlies Knaup Reymond; Didier Le Roy; Thierry Calandra; Gilbert Greub
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-13
Journal Detail:
Title:  Infection and immunity     Volume:  78     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-16     Completed Date:  2010-12-15     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5195-201     Citation Subset:  IM    
Affiliation:
Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chlamydia Infections / immunology,  microbiology,  pathology
Chlamydiales / immunology,  physiology*
Female
Host-Pathogen Interactions / immunology,  physiology
Interleukin-6 / analysis,  blood,  physiology
Lung / chemistry,  immunology,  pathology
Macrophages / immunology,  microbiology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Myeloid Differentiation Factor 88 / immunology,  physiology*
Phagocytosis / physiology
Pneumonia, Bacterial / immunology,  microbiology,  pathology
Signal Transduction / physiology
Toll-Like Receptor 2 / immunology,  physiology*
Toll-Like Receptor 4 / immunology,  physiology*
Tumor Necrosis Factor-alpha / analysis,  blood,  physiology
Chemical
Reg. No./Substance:
0/Interleukin-6; 0/Myeloid Differentiation Factor 88; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha
Comments/Corrections

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