NEUTROPHILS PRODUCE HIGH LEVELS OF CHEMOKINES (CXCL1/2) AFTER SENSING GROUP B STREPTOCOCCUS THROUGH ENDOSOMAL TLRS

Introduction: Neutrophils have a crucial role in host defenses against Streptococcus agalactiae (Group B Streptococcus, GBS), a leading cause of serious infections in neonates, post-partum women 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 recognition of these bacteria by this cell type. Materials and Methods: Bone-marrow-derived neutrophil preparations were obtained from wild type mice or mice deficient in Toll-like receptors (TLRs) or TLR adaptors/chaperones. Cells were exposed to live GBS and supernatants were collected for cytokine measurements by ELISA. Results: Chemokine (CXCL1 and CXCL2, Chemokine receptor ligand 1 and 2), but not TNF-alpha, production by neutrophils in response to live bacteria was considerably higher than that observed after stimulation with LPS or killed bacteria. This response required the TLR adaptor MyD88 (Myeloid Differentiation factor 88) and UNC93B1, a chaperone protein required for the localization of TLRs to endosomal compartments [2, 3]. Conclusions: Neutrophils play a crucial role in host defenses against GBS infection [1]. Neutrophils have been assigned the role of short-lived effector cells with limited ability to influence the function of other cell types through cytokine production. Our results show that neutrophils produce high levels of CXCL1 and CXCL2 directly in response to GBS through a mechanism that required endosomal TLRs, thereby amplifying their own recruitment 1. Biondo C et al. Infect Immun 2014; 82: 4508-17 2. Tabeta K et al. NatImmunol 2006; 7: 156-64. 3. Biondo C et al. mBio 2014; 5: 01428-01414.