Group A Streptococcus Secreted Esterase Hydrolyzes Platelet-Activating Factor to Impede Neutrophil Recruitment and Facilitate Innate Immune Evasion

Platelet-activating factor Neutrophil Extracellular Traps Platelet-activating factor receptor
DOI: 10.1371/journal.ppat.1002624 Publication Date: 2012-04-05T20:53:32Z
ABSTRACT
The innate immune system is the first line of host defense against invading organisms. Thus, pathogens have developed virulence mechanisms to evade system. Here, we report a novel means for inhibition neutrophil recruitment by Group A Streptococcus (GAS). Deletion secreted esterase gene (designated sse) in M1T1 GAS strains with (MGAS5005) and without (MGAS2221) null covS mutation enhances ingress infection sites skin mice. In trans expression SsE MGAS2221 reduces invasion. sse deletion mutant MGAS5005 (ΔsseMGAS5005) more efficiently cleared from than parent strain. hydrolyzes sn-2 ester bond platelet-activating factor (PAF), converting biologically active PAF into inactive lyso-PAF. KM kcat hydrolysis 2-thio-PAF were similar those human plasma acetylhydrolase. Treatment abolishes capacity induce activation chemotaxis neutrophils. More importantly, receptor-deficient mice significantly reduce infiltration site ΔsseMGAS5005 infection. These findings identify acetylhydrolase bacterial support evasion mechanism that phagocyte inactivating PAF, providing new paradigm responses.
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