Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia.
Pneumocystis pneumonia (PcP) is marked by substantial inflammatory damage to the lung. We have found that Toll-like receptor 2 (TLR2) mediates macrophage inflammatory responses to Pneumocystis and hypothesized that TLR2 deficiency would lead to less severe inflammation and milder lung injury during PcP. Histopathology examination showed that TLR2-/- mice with PcP indeed exhibited milder pulmonary inflammation. TLR2-/- mouse lungs contained less TNF-alpha and displayed lower levels of NF-kappaB activation during PcP. However, TLR2-/- mice with PcP displayed increased severity in symptoms and organism burden. The increased organism burden is likely due to defects in protective mechanisms in TLR2-/- mice. mRNA levels of the inducible nitric oxide synthase and NADPH oxidase p47phox, as well as nitric oxide levels in the lungs, were decreased in TLR2-/- PcP mice. Taken together, this study shows that TLR2-mediated inflammatory responses contribute to a certain degree to the clearance of Pneumocystis organism in mice.
Wang
Shao-Hung
SH
Department of Medical Research, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan, ROC.
Zhang
Chen
C
Lasbury
Mark E
ME
Liao
Chung-Ping
CP
Durant
Pamela J
PJ
Tschang
Dennis
D
Lee
Chao-Hung
CH
D000818:Animals; D005260:Female; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000737:chemistry / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000096:biosynthesis; D016328:NF-kappa B / Q000032:analysis; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D045363:Pneumocystis carinii / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1