Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but\ud limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi),\ud provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface\ud in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal\ud exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing\ud was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in\ud recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils\ud from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed\ud increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp\ud during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate\ud the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo
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