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-α and displayed lower levels of NF-κB 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.