CCR7-deficient mice exhibit a delayed antigen-specific mucosal IgA antibody response to an oral recombinant Salmonella strain

Abstract

ABSTRACT The migration of antigen (Ag)-loading dendritic cells (DCs) from Peyer's patches (PPs) to the draining mesenteric lymph nodes (MLNs) via chemokine receptor 7 (CCR7) is thought to be an important step in the initiation of acquired immunity. Our previous study showed that PPs were indispensable for Ag-specific secretory (S)IgA antibody (Ab) responses against oral recombinant Salmonella (rSalmonella). In this study, we attempted to show direct PP DC migration to MLNs by employing photoconvertible protein transgenic mice and investigated the role of the CCR7 signaling pathway in mucosal IgA induction. Our results demonstrated an actual flux of DCs from PPs to MLNs. The frequency of CCR7+ CD11c+ DCs in MLNs of PP-deficient mice was reduced, suggesting that some PP DCs migrated via CCR7. Immunization of CCR7−/− mice elicited significantly lower levels of Ag-specific SIgA Ab responses, which was associated with diminished formation of the germinal center in PPs. However, increased SIgA Ab production and dissemination of rSalmonella were observed at later time points. These results suggest that, although CCR7 was required for SIgA induction at normal velocity, the CCR7-mediated pathway is not essential for the induction of Ag-specific SIgA Ab responses to rSalmonella.