αvβ8 integrin-expression by BATF3-dependent dendritic cells facilitates early IgA responses to Rotavirus
Joy Nakawesi, Sébastien This, Julia Hütter, Mathilde Boucard-Jourdin, Véronique Barateau, Konjit Getachew Muleta, L.J. Gooday, Kirsten Thomsen, Agnès Garcias López, Isabel Ulmert, Didier Poncet, Bernard MALISSEN, Harry B. Greenberg, Olivier Thaunat, Thierry Defrance, Helena Païdassi, Katharina Lahl
Abstract
Secretory intestinal IgA can protect from re-infection with rotavirus (RV), but very little is known about the mechanisms that induce IgA production during intestinal virus infections. Classical dendritic cells (cDCs) in the intestine can facilitate both T cell-dependent and -independent secretory IgA. Here, we show that BATF3-dependent cDC1, but not cDC2, are critical for the optimal induction of RV-specific IgA responses in the mesenteric lymph nodes. This depends on the selective expression of the TGFβ-activating integrin αvβ8 by cDC1. In contrast, αvβ8 on cDC1 is dispensible for steady state immune homeostasis. Given that cDC2 are crucial in driving IgA during steady state but are dispensable for RV-specific IgA responses, we propose that the capacity of DC subsets to induce intestinal IgA responses reflects the context, as opposed to an intrinsic property of individual DC subsets.