Interplay Of Plasmacytoid And Conventional cDC1 In The Secretory IgA Response To Rotavirus

Rotavirus (RV), a double-stranded RNA-virus, primarily infects the small intestinal epithelium. RV specific secretory IgA is sufficient to mediate long-term protection from reinfection and resolution of primary infection in mice and likely in humans. Dendritic cells (DCs) guide the initiation of adaptive immunity. We have previously shown that plasmacytoid dendritic cells (pDCs) are necessary for optimal RV-specific IgA induction following infection, a process depending on the production of type I IFNs by pDCs. We now show that BATF3 deficient mice lacking CD103⁺CD11b^- conventional dendritic cells (intestinal cDC1 DCs) also show diminished RV-specific IgA responses, suggesting a role for these accessory cells in viral clearance through humoral immunity induction. Interestingly, full activation of cDC1 conventional dendritic cells in response to RV infection depends on both pDCs and TLR3. The gut is a highly immune challenged organ, requiring careful fine-tuning of immune responses to avoid inflammation in the absence of pathogens. A dual requirement for 1) cDC stimulation by type I IFNs from responding pDCs, and 2) simultaneous direct TLR signaling within cDC for full cDC activation in response to RV may function as a safety net to avoid aberrant inflammation of the gut wall.