CXCL1/2 chemokines are newly synthesized by neutrophils and released at high levels after recognition of live Group B Streptococcus by means of endosomal Toll-like receptors

Purpose: Neutrophil function is crucial in host defenses against Streptococcus agalactiae (Group B Streptococcus, GBS), a leading cause of infections in neonates and elderly people [1]. Since little is known about anti-GBS responses in neutrophils here we studied the mechanism underlying chemokine production after innate immune recognitionof these bacteria. Methods: Neutrophils were isolated from the bone marrow of wild type mice or animals with genetic defects in Toll-like receptors (TLRs) or TLR adaptors/chaperones. Cells were cultured in the presence of live GBS. Supernatants were collected for cytokine measurements by ELISA. Results: Neutrophils produced CXCL1and CXCL2 (Chemokine receptor ligand 1 and 2) in response to live bacteria at levels far exceeding those observed after stimulation with LPS or killed bacteria. Chemokine production required signaling through the TLR adaptor MyD88 (Myeloid Differentiation factor 88) and functional UNC93B1, a chaperone protein involved in recruitment of nucleic acid sensing TLRs to the endosomes [2, 3]. Lack of single TLRs had no effect on chemokine production. Discussion: Neutrophil recruitment plays a crucial role in GBS infection [1]. These cells have long been considered as short-lived and unable to orchestrate immune responses through cytokine production. Here we show that neutrophils abundantly produce CXCL1 and CXCL2 directly in response to GBS by TLR-dependent mechanism. Conclusions: Neutrophils directly recognize GBS by means of endosomal TLRs. These cells can amplify their own recruitment through the synthesis of CXCL1 and CXCL2 directly after GBS recognition. Bibliography 1. Biondo C. et al. Infect Immun 2014; 82: 4508-17. 2. Tabeta K. et al. NatImmuno 2006; l7: 156-64. 3. Biondo C. et al. mBio 2014; 5: 01428-01414.