Role of MyD88 and Toll-like receptors 2 and 4 in the sensing of Parachlamydia acanthamoebae.
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.
Roger
Thierry
T
Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Casson
Nicola
N
Croxatto
Antony
A
Entenza
José Manuel
JM
Pusztaszeri
Marc
M
Akira
Shizuo
S
Reymond
Marlies Knaup
MK
Le Roy
Didier
D
Calandra
Thierry
T
Greub
Gilbert
G
D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002695:Chlamydiales / Q000276:immunology / Q000502:physiology*; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood / Q000502:physiology; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood / Q000502:physiology
D015850:Interleukin-6; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha