The Legionella pneumophila EnhC protein interferes with immunostimulatory muramyl peptide production to evade innate immunity.

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02115, USA.
Cell host & microbe (Impact Factor: 12.19). 08/2012; 12(2):166-76. DOI: 10.1016/j.chom.2012.06.004
Source: PubMed

ABSTRACT Successful pathogens have evolved to evade innate immune recognition of microbial molecules by pattern recognition receptors (PRR), which control microbial growth in host tissues. Upon Legionella pneumophila infection of macrophages, the cytosolic PRR Nod1 recognizes anhydro-disaccharide-tetrapeptide (anhDSTP) generated by soluble lytic transglycosylase (SltL), the predominant bacterial peptidoglycan degrading enzyme, to activate NF-κB-dependent innate immune responses. We show that L. pneumophila periplasmic protein EnhC, which is uniquely required for bacterial replication within macrophages, interferes with SltL to lower anhDSTP production. L. pneumophila mutant strains lacking EnhC (ΔenhC) increase Nod1-dependent NF-κB activation in host cells, while reducing SltL activity in a ΔenhC strain restores intracellular bacterial growth. Further, L. pneumophila ΔenhC is specifically rescued in Nod1- but not Nod2-deficient macrophages, arguing that EnhC facilitates evasion from Nod1 recognition. These results indicate that a bacterial pathogen regulates peptidoglycan degradation to control the production of PRR ligands and evade innate immune recognition.

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Available from: James T Park, Oct 06, 2014
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    • "NOD engagement of PAMPs activates receptor interacting serine/threonine kinase (RICK), resulting in activation of NFkB-mediated transcription (Kersse et al., 2011) (Fig. 2). Several bacteria modify peptidoglycan in order to avoid being recognized by NODs (Wolfert et al., 2007), and Legionella pneumophila encodes a periplasmic protein EnhC that inhibits degradation of peptidoglycan thereby preventing production of PAMPs (Liu et al., 2012). A third approach is to inhibit TLR signalling by direct interactions between secreted bacterial effector molecules and the host TLR receptors. "
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