Macrophages pulsed with intact Streptococcus pneumoniae play an active role as antigen‐presenting cells in eliciting an anti‐protein response upon adoptive transfer into naïve mice

Macrophages, in contrast to dendritic cells (DC) are regarded as ineffective for priming naïve CD4+ T cells, but the relative role of these cells in promoting T cell‐dependent humoral immunity in a naïve host is largely unknown. We isolated bone marrow‐derived (BMM) and peritoneal (PerM) macrophages, as well as bone marrow‐derived DC (BMDC) and pulsed them with intact S. pneumoniae (Pn) followed by transfer into naive WT mice. Both Pn14‐pulsed BMM and PerM, elicited an IgM and/or IgG anti‐protein and anti‐polysaccharide (PS) response comparable to that of BMDC. Whereas the IgG anti‐protein response by Pn‐pulsed BMM exhibited an absolute requirement for T cells in the recipient, the induced anti‐PS response was largely T cell‐independent. Nevertheless, in vitro, Pn‐pulsed BMDC secreted significantly more pro‐ and anti‐inflammatory cytokines, underwent a greater degree of phenotypic maturation, and presented pneumococcal surface protein A (PspA) to a PspA‐specific T hybridoma more efficiently than either BMM or PerM. Pn‐pused BMM that were paraformaldehyde‐fixed prior to transfer or lacking expression of CD40 or MHC‐II failed to elicit an anti‐protein response, although the anti‐PS response was largely unaffected. These data are the first to demonstrate that macrophages can play an active role as APCs for eliciting a protein‐specific Ig response in vivo in a naïve host. Supported by NIH grant 2R01 AI49192