Nod1 Signaling Overcomes Resistance of S. pneumoniae to Opsonophagocytic Killing

• DOI: 10.1371/journal.ppat.0030118
• Publication Date: 2007-08-20T18:43:14Z
• Authors: Elena S Lysenko; Thomas B Clarke; Mikhail Shchepetov; Adam J Ratner; David I Roper; Christopher G Dowson; Jeffrey N Weiser
• Keywords: QH301-705.5; Neutrophils; Peptidoglycan; Mice; Mice, Congenic; 03 medical and health sciences; Phagocytosis; Nod1 Signaling Adaptor Protein; Animals; Humans; Gene Silencing; Biology (General); Adaptor Proteins, Signal Transducing; Mice, Knockout; 0303 health sciences; RC581-607; Opsonin Proteins; Pneumonia, Pneumococcal; Immunity, Innate; QR; 3. Good health; Mice, Inbred C57BL; Streptococcus pneumoniae; Neutrophil Infiltration; Immunologic diseases. Allergy; Research Article; Signal Transduction

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