Toll-like receptor 9 is not important for host defense against Haemophilus influenzae.
Non-typeable Haemophilus influenzae (NTHi) is a common Gram-negative respiratory pathogen. We demonstrated previously that myeloid differentiation primary-response protein 88 (MyD88) is of utmost importance in host defense against NTHi. All TLRs except for TLR3 depend on MyD88 for signaling. TLR9, the TLR for detecting pathogen DNA depends on MyD88 signaling. Here, we investigate the role of TLR9 during NTHi pneumonia. Alveolar macrophages (AM) from normal wild-type (WT) and TLR9 knock-out (KO) mice were harvested and stimulated with growth-arrested NTHi or CPG DNA. WT and TLR9 KO mice were infected intranasally with NTHi: cytokine and chemokine responses were measured 16h later. Despite significant reduced TNF production by TLR9 KO AM in response to CPG DNA, no difference was detected in TNF production after NTHi stimulation by isolated alveolar macrophages from WT and TLR9 KO mice. Moreover, we found similar pulmonary bacterial loads, similar cytokine and chemokine levels in WT and TLR9 KO mice, and no differences in histopathology. In conclusion, we were not able to demonstrate a role for TLR9 in the recognition of and host defense against NTHi.
Wieland
Catharina W
CW
Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, The Netherlands. c.wieland@amc.uva.nl
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D002478:Cells, Cultured; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae; D007113:Immunity, Innate; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000276:immunology*; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D053594:Myeloid Differentiation Factor 88; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha