αvβ8 integrin-expression by BATF3-dependent dendritic cells facilitates early IgA responses to Rotavirus.

J Nakawesi,S This,H Paidassi,O Thaunat,I Ulmert,H Greenberg,K Lahl,L.J Gooday,D Poncet,J Hütter,B Malissen,K Fog Thomsen,V Barateau,K Getachew Muleta,M Boucard-Jourdin,T Defrance,A Garcias López

doi:10.1038/s41385-020-0276-8

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.

Highlights

Rotavirus (RV) is a double-stranded RNA virus that replicates in mature enterocytes at the tips of the small intestinal villi[1,2] and was first identified by electron microscopy in intestinal biopsies of children diagnosed with acute gastroenteritis.[3]
Because antibodies play a major role in protection of infants from RV-reinfection,[38] we sought to explore the cellular requirements for required for RV-specific IgA responses. huCD207.DTA mice lack small intestinal CD103+ cDC2 and Langerhans cells[42] and when infected orally with RV, these mice generated total and VLP+IgA+ B cell responses in mLNs that were
In order to assess shedding of RV or in the levels of fecal RV-specific IgA. These results indicate that Batf3-dependent CD103+CD11b− DCs (cDC1) are required for the optimal induction of anti-RV-specific IgA+ plasmablasts in the mLNs, while cDC2 are dispensable

Summary

Introduction

Rotavirus (RV) is a double-stranded RNA virus that replicates in mature enterocytes at the tips of the small intestinal villi[1,2] and was first identified by electron microscopy in intestinal biopsies of children diagnosed with acute gastroenteritis.[3]. Most of the anti-RV response in intact animals requires T cell help.[8]

Methods

Results

Conclusion