Autor(es):
Papotto, Pedro H. ; Yilmaz, Bahtiyar ; Pimenta, Gonçalo ; Mensurado, Sofia ; Cunha, Carolina ; Fiala, Gina ; Gomes Da Costa, Daniel ; Gonçalves-Sousa, Natacha ; Chan, Brian H. K. ; Blankenhaus, Birte ; Domingues, Rita G. ; Carvalho, Tânia ; Hepworth, Matthew R. ; Macpherson, Andrew J. ; Allen, Judith E. ; Silva-Santos, Bruno
Data: 2023
Identificador Persistente: http://hdl.handle.net/10451/65467
Origem: Repositório da Universidade de Lisboa
Assunto(s): Immunology; Microbiology; Gut-lung axis; Helminth infection; Innate lymphoid cells; Maternal; Microbiota; Neonatal; Short-chain fatty acids; Type 2 immunity; γδT cells
Descrição
Immune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared with the progeny of γδ T cell-sufficient dams. Upon helminth infection, mice born from TCRδ-/- dams sustain an increased type 2 inflammatory response. This is independent of the genotype of the pups. Instead, the offspring of TCRδ-/- dams harbors a distinct intestinal microbiota, acquired during birth and fostering, and decreased levels of intestinal short-chain fatty acids (SCFAs), such as pentanoate and hexanoate. Importantly, exogenous SCFA supplementation inhibits type 2 innate lymphoid cell function and suppresses first-breath- and infection-induced inflammation. Taken together, our findings unravel a maternal γδ T cell-microbiota-SCFA axis regulating neonatal lung immunity.
