title: Inflammatory monocytes are critical for induction of a polysaccharide-specific antibody response to an intact bacterium.
abstract: Although inflammatory monocytes (IM) (CD11b(+)Ly6C(hi) cells) have been shown to play important roles in cell-mediated host protection against intracellular bacteria, protozoans, and fungi, their potential impact on humoral immune responses to extracellular bacteria are unknown. IM, localized largely to the splenic marginal zone of naive CD11b-diphtheria toxin (DT) receptor bone marrow-chimeric mice were selectively depleted following treatment with DT, including no reduction of CD11b(+) peritoneal B cells. Depletion of IM resulted in a marked reduction in the polysaccharide (PS)-specific, T cell-independent IgM, and T cell-dependent IgG responses to intact, heat-killed Streptococcus pneumoniae with no effect on the associated S. pneumoniae protein-specific IgG response or on the PS- and protein-specific IgG responses to a soluble pneumococcal conjugate vaccine. IM acted largely within the first 48 h following the initiation of the immune response to S. pneumoniae to induce the subsequent production of PS-specific IgM and IgG. Adoptive transfer of highly purified IM from wild-type mice into DT-treated CD11b-DT receptor mice completely restored the defective PS-specific Ig response to S. pneumoniae. IM were phenotypically and functionally distinct from circulating CD11b(+)CD11c(low)Ly6G/C cells (immature blood dendritic cells), previously described to play a role in Ig responses to S. pneumoniae, in that they were CD11c(-) as well as Ly6C(hi) and did not internalize injected S. pneumoniae during the early phase of the response. These data are the first, to our knowledge, to establish a critical role for IM in the induction of an Ig response to an intact extracellular bacterium.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Chen
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D000950:Antigens, Ly / Q000032:analysis; D016667:Bacterial Capsules / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D039481:CD11b Antigen / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D004167:Diphtheria Toxin / Q000633:toxicity; D004705:Endocytosis; D066257:Heparin-binding EGF-like Growth Factor; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000145:classification / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000276:immunology; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000950:Antigens, Ly; D001426:Bacterial Proteins; D039481:CD11b Antigen; D039521:CD11c Antigen; D004167:Diphtheria Toxin; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D036341:Intercellular Signaling Peptides and Proteins; C494192:Ly-6C antigen, mouse; D022242:Pneumococcal Vaccines; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; C056696:pneumococcal polysaccharide, type 14; C051592:pneumococcal surface protein A