CX3CR1+ Macrophages and CD8+ T Cells Control Intestinal IgA Production

Secretory IgA is a key host defense mechanism that controls the intestinal microbiota. We investigated the role of CD11c(+)CX(3)CR1(+)CD64(+) macrophages in IgA production in the intestine. Intestinal CX(3)CR1(+) macrophages directly induced IgA secretion by B cells. Ag delivery to lamina propria (LP) CX(3)CR1(+) macrophages specifically induced intestinal IgA production. The induction of IgA by CX(3)CR1(+) macrophages required BAFF, a proliferation-inducing ligand, and TNF-alpha, but was surprisingly independent of TLR-mediated microbial recognition and retinoic acid signaling. IgA secretion by CX(3)CR1(+) macrophages was enhanced by LP CD8(+) T cells through the secretion of IL-9 and IL-13. CX(3)CR1(+) macrophages and CD8(+) T cells induced IgA production by B cells independently of mesenteric lymph nodes and Peyer patches. Our data reveal a previously unrecognized cellular circuitry in which LP CX(3)CR1(+) macrophages, B cells, and CD8(+) T cells coordinate the protective Ig secretion in the small intestine upon peripheral Ag delivery.