Nucleotide-binding oligomerization domain containing-like receptor family, caspase recruitment domain (CARD) containing 4 (NLRC4) regulates intrapulmonary replication of aerosolized Legionella pneumophila

BMC Infectious Diseases

Thomas R Hawn¹  Shawn J Skerrett¹  Kelly D Smith¹  William R Berrington¹ 

[1]Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356423, Seattle, Washington, 98195-6523, USA

关键词: TLR5;    NLRC4;    Alveolar macrophage;    Pneumonia;    Legionella pneumophila;   

Others  :  1146336
DOI  :  10.1186/1471-2334-13-371

 received in 2013-03-19, accepted in 2013-08-08,  发布年份 2013

【 摘 要 】

Background

Legionella pneumophila (Lp) flagellin activates signaling pathways in murine macrophages that control Lp replication. Nucleotide-binding oligomerization domain (NOD) containing-like receptor (NLR) family, caspase recruitment domain (CARD) containing 4 (NLRC4) and Toll-like Receptor (TLR5) both recognize Lp flagellin in vitro, but whether these two receptors play redundant or separate functional roles in vivo is unknown.

Methods

The immune response of Nlrc4−/−, Nlrc4−/−/Tlr5−/−, and wild type C57Bl/6 mice was analyzed after in vivo infection with aerosolized Lp.

Results

Lp clearance from the lungs was delayed in Nlrc4−/− mice over seven days in comparison to wild type controls. Nlrc4−/−/Tlr5−/− mice had no additional defect. In contrast to TLR5, NLRC4 did not regulate recruitment of neutrophils to the lung. Although there were no differences among the mouse strains in the lung transcriptome at 4 hours, Nlrc4−/− and Nlrc4−/−Tlr5−/− mice had increased lung inflammation at 72 hours in comparison to WT. Nlrc4−/−/Tlr5−/− mice also had altered cytokine production at both 4 and 24 hours post infection when compared to wild-type (WT) and Nlrc4−/− mice. Lp replication in murine alveolar macrophages was NLRC4-dependent and TLR5-independent.

Conclusion

These studies reveal that NLRC4 and TLR5 mediate different roles in the inflammatory response to Lp flagellin in an aerosolized infection model and NLRC4 regulates replication in both lungs and alveolar macrophages.

【 授权许可】

   
2013 Berrington et al.; licensee BioMed Central Ltd.

【 图 表 】

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