| First Author | Biswas D | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 9 | Pages | 108766 |
| PubMed ID | 33657368 | Mgi Jnum | J:324655 |
| Mgi Id | MGI:6716803 | Doi | 10.1016/j.celrep.2021.108766 |
| Citation | Biswas D, et al. (2021) LL-37-mediated activation of host receptors is critical for defense against group A streptococcal infection. Cell Rep 34(9):108766 |
| abstractText | Group A Streptococcus (GAS) causes diverse human diseases, including life-threatening soft-tissue infections. It is accepted that the human antimicrobial peptide LL-37 protects the host by killing GAS. Here, we show that GAS extracellular protease ScpC N-terminally cleaves LL-37 into two fragments of 8 and 29 amino acids, preserving its bactericidal activity. At sub-bactericidal concentrations, the cleavage inhibits LL-37-mediated neutrophil chemotaxis, shortens neutrophil lifespan, and eliminates P2X7 and EGF receptors' activation. Mutations at the LL-37 cleavage site protect the peptide from ScpC-mediated splitting, maintaining all its functions. The mouse LL-37 ortholog CRAMP is neither cleaved by ScpC nor does it activate P2X7 or EGF receptors. Treating wild-type or CRAMP-null mice with sub-bactericidal concentrations of the non-cleavable LL-37 analogs promotes GAS clearance that is abolished by the administration of either P2X7 or EGF receptor antagonists. We demonstrate that LL-37-mediated activation of host receptors is critical for defense against GAS soft-tissue infections. |
