Group A streptococcal M1 protein sequesters cathelicidin to evade innate immune killing

Cathelicidins are cationic antimicrobial peptides produced by leukocytes and epithelial cells that provide a critical first line of defense against microbial invasion (Wong et al., 2013, Nizet et al., 2001). Cathelicidin expression is strongly induced during infection and injury (Dorschner et al., 2001), initially as a full-length protein that lacks antimicrobial activity (Zaiou et al., 2003). Neutrophil proteinase-3 and keratinocyte kallikreins process cathelicidin to liberate antimicrobial peptides derived from its carboxyl terminus (Murakami et al., 2004, S?rensen et al., 2001, Yamasaki et al., 2006). Some cathelicidin peptides, the best characterized being human LL-37, also function as signaling molecules to stimulate inflammation (Yamasaki et al., 2007), production of other antimicrobials (Alalwani et al., 2010), chemotaxis (De Yang et al., 2000), and formation of neutrophil extracellular traps (NETs) (Neumann et al., 2014).