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Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing

By Elena S. Lysenko, Thomas B. Clarke, Mikhail Shchepetov, Adam J. Ratner, David I. Roper, Christopher G. Dowson and Jeffrey N. Weiser

Abstract

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

Topics: QR
Publisher: Public Library of Science
Year: 2007
OAI identifier: oai:wrap.warwick.ac.uk:4437

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