Inflammatory monocytes are critical for induction of a polysaccharide-specific antibody response to an intact bacterium (P3046)

Abstract

Abstract Although inflammatory monocytes (IM) [CD11b+Ly6Chi] play important roles in cell-mediated host protection against intracellular pathogens, their impact on humoral immune responses to extracellular bacteria are unknown. IM, localized largely in the splenic marginal zone of naïve CD11b-Diphtheria toxin receptor (DTR) bone marrow chimeric mice, were selectively depleted following treatment with DT, including no reduction of peritoneal B1a or B1b cells, which express CD11b. Depletion of IM resulted in a marked reduction in the polysaccharide (PS)-specific, T cell-independent IgM and T cell-dependent IgG responses to heat-killed Streptococcus pneumoniae (Pn) with no effect on the Pn protein-specific IgG response, or on the PS- and protein-specific IgG responses to a pneumococcal conjugate vaccine. IM acted largely within the first 48 h to induce the subsequent PS-specific IgM and IgG response. Adoptive transfer of highly purified IM from WT mice into DT-treated CD11b-DTR mice restored the PS-specific Ig response to Pn. IM were phenotypically and functionally distinct from circulating CD11b+CD11clowLy6G-/C- cells (i.e. “blood DC”) previously described to play a role in Ig responses to Pn. These data are the first to establish a critical role for IM in the induction of an Ig response to an intact extracellular bacterium.