ILC2s mediate systemic innate protection by priming mucus production at distal mucosal sites

Campbell, Laura and Hepworth, Matthew R and Whittingham-Dowd, Jayde and Thompson, Seona and Bancroft, Allison J and Hayes, Kelly S and Shaw, Tovah N and Dickey, Burton F and Flamar, Anne-Laure and Artis, David and Schwartz, David A and Evans, Christopher M and Roberts, Ian S and Thornton, David J and Grencis, Richard K (2019) ILC2s mediate systemic innate protection by priming mucus production at distal mucosal sites. The Journal of experimental medicine, 216 (12). pp. 2714-2723. ISSN 0022-1007

Abstract

Host immunity to parasitic nematodes requires the generation of a robust type 2 cytokine response, characterized by the production of interleukin 13 (IL-13), which drives expulsion. Here, we show that infection with helminths in the intestine also induces an ILC2-driven, IL-13-dependent goblet cell hyperplasia and increased production of mucins (Muc5b and Muc5ac) at distal sites, including the lungs and other mucosal barrier sites. Critically, we show that type 2 priming of lung tissue through increased mucin production inhibits the progression of a subsequent lung migratory helminth infection and limits its transit through the airways. These data show that infection by gastrointestinal-dwelling helminths induces a systemic innate mucin response that primes peripheral barrier sites for protection against subsequent secondary helminth infections. These data suggest that innate-driven priming of mucus barriers may have evolved to protect from subsequent infections with multiple helminth species, which occur naturally in endemic areas.