Signal inhibitory receptor on leukocytes-1 recognizes bacterial and endogenous amphipathic alpha-helical peptides

Article

关键词: PHENOL-SOLUBLE MODULINS;    STAPHYLOCOCCUS-AUREUS BIOFILMS;    HUMAN CATHELICIDIN LL-37;    ANTIMICROBIAL PEPTIDES;    ANTIBACTERIAL PEPTIDE;    HUMAN SKIN;    EXPRESSION;    KERATINOCYTES;    DETERMINANTS;    INFLAMMATION;   

DOI  :  10.1096/fj.202100812R

来源: SCIE

【 摘 要 】

Signal inhibitory receptor on leukocytes-1 (SIRL-1) is a negative regulator of myeloid cell function and dampens antimicrobial responses. We here show that different species of the genus Staphylococcus secrete SIRL-1-engaging factors. By screening a library of single-gene transposon mutants in Staphylococcus aureus, we identified these factors as phenol-soluble modulins (PSMs). PSMs are amphipathic alpha-helical peptides involved in multiple aspects of staphylococcal virulence and physiology. They are cytotoxic and activate the chemotactic formyl peptide receptor 2 (FPR2) on immune cells. Human cathelicidin LL-37 is also an amphipathic alpha-helical peptide with antimicrobial and chemotactic activities, structurally and functionally similar to alpha-type PSMs. We demonstrate that alpha-type PSMs from multiple staphylococcal species as well as human cathelicidin LL-37 activate SIRL-1, suggesting that SIRL-1 recognizes alpha-helical peptides with an amphipathic arrangement of hydrophobicity, although we were not able to show direct binding to SIRL-1. Upon rational peptide design, we identified artificial peptides in which the capacity to ligate SIRL-1 is segregated from cytotoxic and FPR2-activating properties, allowing specific engagement of SIRL-1. In conclusion, we propose staphylococcal PSMs and human LL-37 as a potential new class of natural ligands for SIRL-1.

【 授权许可】

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