title: MARCO is required for TLR2- and Nod2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx.
abstract: Streptococcus pneumoniae is a common human pathogen that accounts for >1 million deaths every year. Colonization of the nasopharynx by S. pneumoniae precedes pulmonary and other invasive diseases and, therefore, is a promising target for intervention. Because the receptors scavenger receptor A (SRA), macrophage receptor with collagenous structure (MARCO), and mannose receptor (MR) have been identified as nonopsonic receptors for S. pneumoniae in the lung, we used scavenger receptor knockout mice to study the roles of these receptors in the clearance of S. pneumoniae from the nasopharynx. MARCO(-/-), but not SRA(-/-) or MR(-/-), mice had significantly impaired clearance of S. pneumoniae from the nasopharynx. In addition to impairment in bacterial clearance, MARCO(-/-) mice had abrogated cytokine production and cellular recruitment to the nasopharynx following colonization. Furthermore, macrophages from MARCO(-/-) mice were deficient in cytokine and chemokine production, including type I IFNs, in response to S. pneumoniae. MARCO was required for maximal TLR2- and nucleotide-binding oligomerization domain-containing (Nod)2-dependent NF-κB activation and signaling that ultimately resulted in clearance. Thus, MARCO is an important component of anti-S. pneumoniae responses in the murine nasopharynx during colonization.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dorrington
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Roche
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Chauvin
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Tu
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mossman
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
authors.forename: Dawn M E
authors.initials: DM
authors.lastname: Bowdish
mesh_terms: D000818:Animals; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009305:Nasopharynx / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000502:physiology*
chemical_list: C092228:Marco protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2