[PDF][PDF] Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus

D Kretschmer, AK Gleske, M Rautenberg, R Wang… - Cell host & …, 2010 - cell.com
D Kretschmer, AK Gleske, M Rautenberg, R Wang, M Köberle, E Bohn, T Schöneberg
Cell host & microbe, 2010cell.com
Virulence of emerging community-associated methicillin-resistant Staphylococcus aureus
(CA-MRSA) and other highly pathogenic S. aureus strains depends on their production of
phenol-soluble modulin (PSM) peptide toxins, which combine the capacities to attract and
lyse neutrophils. The molecular basis of PSM-stimulated neutrophil recruitment has
remained unclear. Here, we demonstrate that the human formyl peptide receptor 2
(FPR2/ALX), which has previously been implicated in control of endogenous inflammatory …
Summary
Virulence of emerging community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and other highly pathogenic S. aureus strains depends on their production of phenol-soluble modulin (PSM) peptide toxins, which combine the capacities to attract and lyse neutrophils. The molecular basis of PSM-stimulated neutrophil recruitment has remained unclear. Here, we demonstrate that the human formyl peptide receptor 2 (FPR2/ALX), which has previously been implicated in control of endogenous inflammatory processes, senses PSMs at nanomolar concentrations and initiates proinflammatory neutrophil responses to CA-MRSA. Specific blocking of FPR2/ALX or deletion of PSM genes in CA-MRSA severely diminished neutrophil detection of CA-MRSA. Furthermore, a specific inhibitor of FPR2/ALX and of its functional mouse counterpart blocked PSM-mediated leukocyte infiltration in vivo in a mouse model. Thus, the innate immune system uses a distinct FPR2/ALX-dependent mechanism to specifically sense bacterial peptide toxins and detect highly virulent bacterial pathogens. FPR2/ALX represents an attractive target for new anti-infective or anti-inflammatory strategies.
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