1887

Abstract

is an intracellular organism and the major aetiological agent of Legionnaires' disease. Although recent progress has identified Toll-like receptors (TLRs) as receptors for recognition of pathogen-associated molecular patterns in a variety of micro-organisms, understanding the contribution of TLRs to the host response in infection is still limited. This study examined the roles of TLR2 and TLR4 in murine pneumonia and an infection model using bone-marrow-derived macrophages. TLR2-deficient mice, but not TLR4-deficient mice, demonstrated higher lethal sensitivity to pulmonary challenge with than wild-type mice (<0.05). Although no differences in pulmonary bacterial burden were observed among the mouse strains examined, lower values of macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived cytokine and interleukin (IL)-6 and higher IL-12 levels were noted in lung homogenates of TLR2-deficient mice compared with the wild-type control and TLR4-deficient mice. Recruitment of inflammatory cells, particularly neutrophils, was severely disturbed in the lungs of TLR2-deficient mice. Reduced MIP-2 production was demonstrated in bone-marrow-derived macrophages from TLR2-deficient mice in response to live and purified LPS of this strain, but not LPS. These data highlight the involvement and importance of TLR2 in the pathogenesis of pneumonia in mice. The results showed that TLR2-mediated recognition of LPS and subsequent chemokine-dependent cellular recruitment may be a crucial host innate response in pneumonia.

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2007-03-01
2019-09-20
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