{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:41:07Z","timestamp":1790232067332,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Streptococcus pneumoniae is a common human pathogen that accounts for &amp;gt;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\u2212\/\u2212, but not SRA\u2212\/\u2212 or MR\u2212\/\u2212, mice had significantly impaired clearance of S. pneumoniae from the nasopharynx. In addition to impairment in bacterial clearance, MARCO\u2212\/\u2212 mice had abrogated cytokine production and cellular recruitment to the nasopharynx following colonization. Furthermore, macrophages from MARCO\u2212\/\u2212 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\u2013containing (Nod)2-dependent NF-\u03baB 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1202113","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T20:25:41Z","timestamp":1354220741000},"page":"250-258","source":"Crossref","is-referenced-by-count":82,"title":["MARCO Is Required for TLR2- and Nod2-Mediated Responses to\n                    <i>Streptococcus pneumoniae<\/i>\n                    and Clearance of Pneumococcal Colonization in the Murine Nasopharynx"],"prefix":"10.1093","volume":"190","author":[{"given":"Michael G","family":"Dorrington","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8N 3Z5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife M","family":"Roche","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Chauvin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8N 3Z5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyuan","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8N 3Z5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L","family":"Mossman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8N 3Z5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey N","family":"Weiser","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn M E","family":"Bowdish","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8N 3Z5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2025032406203017500_r1","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0140-6736(09)61204-6","article-title":"Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates","volume":"374","author":"O\u2019Brien","year":"2009","journal-title":"Lancet"},{"key":"2025032406203017500_r2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/infdis\/132.1.55","article-title":"Spread of Streptococcus pneumoniae in families. I. Carriage rates and distribution of types","volume":"132","author":"Hendley","year":"1975","journal-title":"J. Infect. Dis."},{"key":"2025032406203017500_r3","doi-asserted-by":"crossref","first-page":"e00040-11","DOI":"10.1128\/mBio.00040-11","article-title":"High levels of recombination among Streptococcus pneumoniae isolates from the Gambia","volume":"2","author":"Donkor","year":"2011","journal-title":"MBio"},{"key":"2025032406203017500_r4","doi-asserted-by":"crossref","first-page":"8882","DOI":"10.1016\/j.vaccine.2011.09.074","article-title":"Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece","volume":"29","author":"Grivea","year":"2011","journal-title":"Vaccine"},{"key":"2025032406203017500_r5","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/S0140-6736(12)60589-3","article-title":"Serotype replacement after pneumococcal vaccination","volume":"379","author":"Hausdorff","year":"2012","journal-title":"Lancet"},{"key":"2025032406203017500_r6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1556\/amicr.58.2011.3.8","article-title":"A marked shift in the serotypes of pneumococci isolated from healthy children in Szeged, Hungary, over a 6-year period","volume":"58","author":"T\u00f3thp\u00e1l","year":"2011","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"2025032406203017500_r7","first-page":"1899","article-title":"Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice","volume":"119","author":"Zhang","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2025032406203017500_r8","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1172\/JCI57761","article-title":"Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice","volume":"121","author":"Davis","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2025032406203017500_r9","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1172\/JCI57762","article-title":"Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice","volume":"121","author":"Nakamura","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2025032406203017500_r10","doi-asserted-by":"crossref","first-page":"5807","DOI":"10.1128\/IAI.72.10.5807-5813.2004","article-title":"Limited role of antibody in clearance of Streptococcus pneumoniae in a murine model of colonization","volume":"72","author":"McCool","year":"2004","journal-title":"Infect. Immun."},{"key":"2025032406203017500_r11","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1073\/pnas.0501254102","article-title":"CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization","volume":"102","author":"Malley","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032406203017500_r12","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1128\/IAI.01125-09","article-title":"Three surface exoglycosidases from Streptococcus pneumoniae, NanA, BgaA, and StrH, promote resistance to opsonophagocytic killing by human neutrophils","volume":"78","author":"Dalia","year":"2010","journal-title":"Infect. Immun."},{"key":"2025032406203017500_r13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1172\/JCI110444","article-title":"A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia","volume":"69","author":"Brown","year":"1982","journal-title":"J. Clin. Invest."},{"key":"2025032406203017500_r14","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0161-5890(03)00108-1","article-title":"Complement resistance mechanisms of streptococci","volume":"40","author":"Jarva","year":"2003","journal-title":"Mol. Immunol."},{"key":"2025032406203017500_r15","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.neures.2010.12.015","article-title":"Olfactory ensheathing cells as putative host cells for Streptococcus pneumoniae: evidence of bacterial invasion via mannose receptor-mediated endocytosis","volume":"69","author":"Macedo-Ramos","year":"2011","journal-title":"Neurosci. Res."},{"key":"2025032406203017500_r16","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1002\/eji.200526216","article-title":"Specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcus pneumoniae infection","volume":"35","author":"Koppel","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"2025032406203017500_r17","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1165\/rcmb.2006-0128OC","article-title":"The macrophage scavenger receptor SR-AI\/II and lung defense against pneumococci and particles","volume":"35","author":"Arredouani","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025032406203017500_r18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1084\/jem.20040731","article-title":"The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles","volume":"200","author":"Arredouani","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032406203017500_r19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.imbio.2004.02.004","article-title":"The role of scavenger receptors in pathogen recognition and innate immunity","volume":"209","author":"Mukhopadhyay","year":"2004","journal-title":"Immunobiology"},{"key":"2025032406203017500_r20","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1182\/blood-2010-03-276733","article-title":"SR-A\/MARCO-mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens","volume":"117","author":"Mukhopadhyay","year":"2011","journal-title":"Blood"},{"key":"2025032406203017500_r21","doi-asserted-by":"crossref","first-page":"18795","DOI":"10.1074\/jbc.M111.224345","article-title":"Pattern recognition scavenger receptor CD204 attenuates Toll-like receptor 4-induced NF-kappaB activation by directly inhibiting ubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6","volume":"286","author":"Yu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2025032406203017500_r22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1286-4579(00)00296-3","article-title":"The macrophage receptor MARCO","volume":"2","author":"Kraal","year":"2000","journal-title":"Microbes Infect."},{"key":"2025032406203017500_r23","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.4049\/jimmunol.175.9.6058","article-title":"MARCO is the major binding receptor for unopsonized particles and bacteria on human alveolar macrophages","volume":"175","author":"Arredouani","year":"2005","journal-title":"J. Immunol."},{"key":"2025032406203017500_r24","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/jlb.36.6.689","article-title":"Opsonin-independent phagocytosis of surface-adherent bacteria by human alveolar macrophages","volume":"36","author":"Lee","year":"1984","journal-title":"J. Leukoc. Biol."},{"key":"2025032406203017500_r25","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1084\/jem.20011576","article-title":"The immune response to pneumococcal proteins during experimental human carriage","volume":"195","author":"McCool","year":"2002","journal-title":"J. Exp. Med."},{"key":"2025032406203017500_r26","doi-asserted-by":"crossref","first-page":"13315","DOI":"10.1128\/JVI.01167-07","article-title":"Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through Toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems","volume":"81","author":"Rasmussen","year":"2007","journal-title":"J. Virol."},{"key":"2025032406203017500_r27","doi-asserted-by":"crossref","first-page":"41613","DOI":"10.1074\/jbc.M207057200","article-title":"Recognition of bacterial capsular polysaccharides and lipopolysaccharides by the macrophage mannose receptor","volume":"277","author":"Zamze","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2025032406203017500_r28","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/ni1569","article-title":"TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta","volume":"9","author":"Kagan","year":"2008","journal-title":"Nat. Immunol."},{"key":"2025032406203017500_r29","doi-asserted-by":"crossref","first-page":"e1000474","DOI":"10.1371\/journal.ppat.1000474","article-title":"MARCO, TLR2, and CD14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis","volume":"5","author":"Bowdish","year":"2009","journal-title":"PLoS Pathog."},{"key":"2025032406203017500_r30","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.4049\/jimmunol.1000989","article-title":"The class A scavenger receptor, macrophage receptor with collagenous structure, is the major phagocytic receptor for Clostridium sordellii expressed by human decidual macrophages","volume":"185","author":"Thelen","year":"2010","journal-title":"J. Immunol."},{"key":"2025032406203017500_r31","doi-asserted-by":"crossref","first-page":"7718","DOI":"10.1128\/IAI.73.11.7718-7726.2005","article-title":"Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model","volume":"73","author":"van Rossum","year":"2005","journal-title":"Infect. Immun."},{"key":"2025032406203017500_r32","doi-asserted-by":"crossref","first-page":"e00016-11","DOI":"10.1128\/mBio.00016-11","article-title":"Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract","volume":"2","author":"Parker","year":"2011","journal-title":"MBio"},{"key":"2025032406203017500_r33","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0882-4010(86)90071-9","article-title":"Role of interferon in streptococcal infection in the mouse","volume":"1","author":"Weigent","year":"1986","journal-title":"Microb. Pathog."},{"key":"2025032406203017500_r34","doi-asserted-by":"crossref","first-page":"23818","DOI":"10.1074\/jbc.M109.033670","article-title":"pH-dependent internalization of muramyl peptides from early endosomes enables Nod1 and Nod2 signaling","volume":"284","author":"Lee","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2025032406203017500_r35","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.4049\/jimmunol.0901660","article-title":"Internalization and coreceptor expression are critical for TLR2-mediated recognition of lipoteichoic acid in human peripheral blood","volume":"185","author":"Bunk","year":"2010","journal-title":"J. Immunol."},{"key":"2025032406203017500_r36","doi-asserted-by":"crossref","first-page":"811","DOI":"10.4049\/jimmunol.1004143","article-title":"Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs","volume":"188","author":"Koppe","year":"2012","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/1\/250\/61773314\/1202113.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/1\/250\/61773314\/1202113.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T19:09:35Z","timestamp":1742929775000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/190\/1\/250\/8003065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1202113","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718144115.793485338","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,1]]},"published":{"date-parts":[[2013,1,1]]}}}