title: The efficacy of pneumococcal capsular polysaccharide-specific antibodies to serotype 3 Streptococcus pneumoniae requires macrophages.
abstract: The efficacy of antibody immunity against Streptococcus pneumoniae stems from the ability of opsonic, serotype (ST)-specific antibodies to pneumococcal capsular polysaccharide (PPS) to facilitate killing of the homologous ST by host phagocytes. However, PPS-specific antibodies have been identified that are protective in mice, but do not promote opsonic killing in vitro, raising the question of how they mediate protection in vivo. To probe this question, we investigated the dependence of antibody efficacy against lethal systemic (intraperitoneal, i.p.) infection with Streptococcus pneumoniae serotype 3 (ST3) on macrophages and neutrophils for the following PPS3-specific monoclonal antibodies (MAbs) in survival experiments in mice using a non-opsonic human IgM (A7), a non-opsonic mouse IgG1 (1E2) and an opsonic mouse IgG1 (5F6). The survival of A7- and PPS3-specific and isotype control MAb-treated neutrophil-depleted and neutrophil-sufficient and macrophage-depleted and macrophage-sufficient mice were determined after i.p. challenge with ST3 strains 6303 and WU2. Neutrophils were dispensable for A7 and the mouse MAbs to mediate protection in this model, but macrophages were required for the efficacy of A7 and optimal mouse MAb-mediated protection. For A7-treated mice, macrophage-depleted mice had higher blood CFU, cytokines and peripheral neutrophil levels than macrophage-sufficient mice, and macrophage-sufficient mice had lower tissue bacterial burdens than control MAb-treated mice. These findings demonstrate that macrophages contribute to opsonic and non-opsonic PPS3-specific MAb-mediated protection against ST3 infection by enhancing bacterial clearance and suggest that neutrophils do not compensate for the absence of macrophages in the model used in this study.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fabrizio
authors.forename: Catherine
authors.initials: C
authors.lastname: Manix
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Liise-anne
authors.initials: LA
authors.lastname: Pirofski
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D058491:Bacterial Load; D016207:Cytokines / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D011135:Polysaccharides, Bacterial / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial
references.citation: Clin Vaccine Immunol. 2010 May;17(5):713-21
references.pmid: 20200186
references.citation: Infect Immun. 2009 Jan;77(1):464-71
references.pmid: 19001076
references.citation: Infect Immun. 2009 Jan;77(1):485-91
references.pmid: 19001080
references.citation: Infect Immun. 2007 Mar;75(3):1196-202
references.pmid: 17210665
references.citation: Eur J Immunol. 2007 Dec;37(12):3540-50
references.pmid: 18000956
references.citation: J Immunol. 1999 Feb 1;162(3):1685-91
references.pmid: 9973430
references.citation: J Clin Invest. 2006 Oct;116(10):2817-26
references.pmid: 17016562
references.citation: Infect Immun. 2005 Aug;73(8):4530-8
references.pmid: 16040964
references.citation: Infect Immun. 2010 Jul;78(7):3129-35
references.pmid: 20439480
references.citation: Clin Exp Immunol. 2005 May;140(2):230-40
references.pmid: 15807846
references.citation: J Immunol. 2008 Apr 1;180(7):4865-74
references.pmid: 18354210
references.citation: Infect Immun. 2002 Sep;70(9):4977-86
references.pmid: 12183544
references.citation: Infect Immun. 2002 Aug;70(8):4226-38
references.pmid: 12117931
references.citation: Rev Infect Dis. 1983 Sep-Oct;5 Suppl 4:S797-805
references.pmid: 6356294
references.citation: Trends Immunol. 2004 Mar;25(3):143-9
references.pmid: 15036042
references.citation: J Immunol. 2001 Apr 1;166(7):4604-11
references.pmid: 11254718
references.citation: J Exp Med. 1981 Mar 1;153(3):694-705
references.pmid: 7252411
references.citation: Clin Diagn Lab Immunol. 2000 Mar;7(2):314-7
references.pmid: 10702513
references.citation: Scand J Infect Dis. 2003;35(9):647-52
references.pmid: 14620149
references.citation: Infect Immun. 2007 Apr;75(4):1586-97
references.pmid: 17296760
references.citation: Clin Diagn Lab Immunol. 1997 Jul;4(4):415-22
references.pmid: 9220157
references.citation: J Infect Dis. 1980 Dec;142(6):903-9
references.pmid: 7462698
references.citation: Clin Vaccine Immunol. 2007 Apr;14(4):382-90
references.pmid: 17301214
references.citation: Nat Immunol. 2000 Nov;1(5):441-6
references.pmid: 11062505
references.citation: J Surg Res. 2011 May 15;167(2):e131-6
references.pmid: 19691988
references.citation: J Exp Med. 2007 Jun 11;204(6):1319-25
references.pmid: 17548523
references.citation: Infect Immun. 2009 Apr;77(4):1502-13
references.pmid: 19168739
references.citation: Nature. 2006 Nov 9;444(7116):217-20
references.pmid: 17051150
references.citation: Clin Diagn Lab Immunol. 1999 Jul;6(4):581-6
references.pmid: 10391867
references.citation: J Exp Med. 2004 Mar 1;199(5):717-23
references.pmid: 14981111
references.citation: J Immunol. 2008 May 1;180(9):6246-54
references.pmid: 18424747
references.citation: Cell. 2006 Mar 10;124(5):915-27
references.pmid: 16530040
references.citation: Mol Immunol. 2008 Oct;45(16):4041-7
references.pmid: 18752851
references.citation: J Immunol Methods. 1994 Sep 14;174(1-2):83-93
references.pmid: 8083541
references.citation: Infect Immun. 2007 Apr;75(4):1643-50
references.pmid: 17220309
references.citation: Infect Immun. 2005 Jan;73(1):114-25
references.pmid: 15618146
references.citation: Microb Pathog. 2004 Oct;37(4):169-75
references.pmid: 15458777
references.citation: Clin Vaccine Immunol. 2009 May;16(5):636-45
references.pmid: 19279169
references.citation: J Immunol. 2005 Sep 1;175(5):3244-51
references.pmid: 16116215
references.citation: J Immunol. 2004 Mar 1;172(5):3132-8
references.pmid: 14978119
references.citation: Innate Immun. 2009 Feb;15(1):3-12
references.pmid: 19201820
references.citation: Immunity. 1999 Oct;11(4):443-51
references.pmid: 10549626
references.citation: Am J Respir Crit Care Med. 2003 Jan 15;167(2):171-9
references.pmid: 12406830
references.citation: Clin Vaccine Immunol. 2006 Feb;13(2):165-9
references.pmid: 16467321
references.citation: Antimicrob Agents Chemother. 1993 Feb;37(2):234-9
references.pmid: 8452353
references.citation: Eur J Immunol. 2009 Apr;39(4):1147-56
references.pmid: 19266484
references.citation: Clin Vaccine Immunol. 2006 Apr;13(4):459-66
references.pmid: 16603613
references.citation: J Clin Invest. 2009 Jul;119(7):1899-909
references.pmid: 19509469
references.citation: Nature. 1981 Nov 5;294(5836):88-90
references.pmid: 6170000
references.citation: Infect Immun. 1999 Sep;67(9):4517-24
references.pmid: 10456894