Intestinal bacteria condition dendritic cells to promote IgA production.
Immunoglobulin (Ig) A represents the predominant antibody isotype produced at the intestinal mucosa, where it plays an important role in limiting the penetration of commensal intestinal bacteria and opportunistic pathogens. We show in mice that Peyer's Patch-derived dendritic cells (PP-DC) exhibit a specialized phenotype allowing the promotion of IgA production by B2 cells. This phenotype included increased expression of the retinaldehyde dehydrogenase 1 (RALDH1), inducible nitric oxide synthase (iNOS), B cell activating factor of the tumor necrosis family (BAFF), a proliferation-inducing ligand (APRIL), and receptors for the neuropeptide vasoactive intestinal peptide (VIP). The ability of PP-DC to promote anti-CD40 dependent IgA was partially dependent on retinoic acid (RA) and transforming growth factor (TGF)-beta, whilst BAFF and APRIL signaling were not required. Signals delivered by BAFF and APRIL were crucial for CD40 independent IgA production, although the contribution of B2 cells to this pathway was minimal. The unique ability of PP-DC to instruct naïve B cells to differentiate into IgA producing plasma cells was mainly imparted by the presence of intestinal commensal bacteria, and could be mimicked by the addition of LPS to the culture. These data indicate that exposure to pathogen-associated molecular patterns present on intestinal commensal bacteria condition DC to express a unique molecular footprint that in turn allows them to promote IgA production.
Massacand
Joanna C
JC
Environmental Biomedicine, Institute of Integrative Biology, Swiss Federal Institute of Technology, Zürich-Schlieren, Switzerland.
Kaiser
Patrick
P
Ernst
Bettina
B
Tardivel
Aubry
A
Bürki
Kurt
K
Schneider
Pascal
P
Harris
Nicola L
NL
D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology; D007421:Intestine, Small / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology; D010641:Phenotype
D007070:Immunoglobulin A