Lysenko, Elena S., Clarke, Thomas B., Shchepetov, Mikhail, Ratner, Adam J., Roper, David I., Dowson, Christopher G. and Weiser, Jeffrey N. (2007) Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing. PL o S Pathogens , Vol.3 (No.8). pp. 1073-1081. doi:10.1371/journal.ppat.0030118 ISSN 1553-7366.

Preview

PDF WRAP_Dowson_Nod!_signaling.pdf - Requires a PDF viewer. Download (456Kb)

Request Changes to record.

Abstract

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 γ-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.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Streptococcus pneumoniae, Neutrophils -- Immunology, Inflammation -- Immunological aspects, Haemophilus influenzae
Journal or Publication Title:	PL o S Pathogens
Publisher:	Public Library of Science
ISSN:	1553-7366
Official Date:	24 August 2007
Dates:	Date Event 24 August 2007 Published
Volume:	Vol.3
Number:	No.8
Page Range:	pp. 1073-1081
DOI:	10.1371/journal.ppat.0030118
Status:	Peer Reviewed
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), United States. Public Health Service (PHS), University of Pennsylvania. School of Medicine, Pediatric Infectious Diseases Society, St. Jude Children's Research Hospital
Grant number:	AI44231 (PHS), AI05467 (PHS), AI38446 (PHS), AI065450 (PHS), P30 DK50306 (Penn)

Request changes or add full text files to a record

Repository staff actions (login required)

View Item