Myeloid differentiation primary response gene (88)- and toll-like receptor 2-deficient mice are susceptible to infection with aerosolized Legionella pneumophila - PubMed (original) (raw)
. 2006 Jun 15;193(12):1693-702.
doi: 10.1086/504525. Epub 2006 May 11.
Affiliations
- PMID: 16703513
- DOI: 10.1086/504525
Myeloid differentiation primary response gene (88)- and toll-like receptor 2-deficient mice are susceptible to infection with aerosolized Legionella pneumophila
Thomas R Hawn et al. J Infect Dis. 2006.
Abstract
Background: Toll-like receptors (TLRs) are a family of proteins that orchestrate innate immune responses to microbes. Although pathogens are typically recognized by multiple TLRs, the specific roles of individual TLRs in mediating host protection during in vivo infection are not well understood.
Methods: We compared the roles of myeloid differentiation primary response gene (88) (MyD88), which regulates signaling through multiple TLRs, and TLR2 in mediating resistance to aerosolized Legionella pneumophila infection in vivo.
Results: In comparison with wild-type mice, MyD88-deficient (MyD88(-/-)) mice had dramatically higher bacterial counts in the lungs, with decreased neutrophil counts in the bronchoalveolar lavage fluid as well as absent cytokine and chemokine production at early time points. By day 6 of infection, the MyD88(-/-) mice developed organizing pneumonia with dissemination of L. pneumophila to the lymph nodes and spleen. TLR2(-/-) mice were also more susceptible to L. pneumophila, with higher bacterial counts in the lung. However, TLR2(-/-) mice produced proinflammatory cytokines, recruited neutrophils to the lung alveoli, and cleared the infection without progression to organizing pneumonia and disseminated disease.
Conclusions: These results suggest that a MyD88-dependent pathway is required for eradication of L. pneumophila and prevention of organizing pneumonia. TLR2 mediates partial resistance to L. pneumophila, which indicates that additional MyD88-dependent, TLR2-independent pathways are essential for full protection.
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