Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity.

Autor:	Karo-Atar D; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, Quebec, Canada.; McGill Regenerative Medicine Network, Montreal, Quebec, Canada., Ouladan S; Department of Pathology, McGill University and Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.; McGill Regenerative Medicine Network, Montreal, Quebec, Canada., Javkar T; Department of Pathology, McGill University and Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.; McGill Regenerative Medicine Network, Montreal, Quebec, Canada., Joumier L; Division of Systems Biology, Montreal Clinical Research Institute, Montreal, QC, Canada.; Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, Quebec, Canada., Matheson MK; Department of Immunology, University of Washington, Seattle, WA., Merritt S; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada., Westfall S; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada., Rochette A; Department of Pathology, McGill University and Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.; McGill Regenerative Medicine Network, Montreal, Quebec, Canada., Gentile ME; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada., Fontes G; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada., Fonseca GJ; McGill University Health Centre, Meakins-Christie Laboratories, Department of Medicine, Division of Quantitative Life Sciences, Montreal, Quebec, Canada., Parisien M; Department of Human Genetics, Allen Edwards Centre for Pain Research, McGill University, Montreal, Quebec, Canada., Diatchenko L; Department of Human Genetics, Allen Edwards Centre for Pain Research, McGill University, Montreal, Quebec, Canada., von Moltke J; Department of Immunology, University of Washington, Seattle, WA., Malleshaiah M; Division of Systems Biology, Montreal Clinical Research Institute, Montreal, QC, Canada.; Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, Quebec, Canada.; McGill Regenerative Medicine Network, Montreal, Quebec, Canada., Gregorieff A; Department of Pathology, McGill University and Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.; McGill Regenerative Medicine Network, Montreal, Quebec, Canada., King IL; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, Quebec, Canada.; McGill Regenerative Medicine Network, Montreal, Quebec, Canada.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Sep 05; Vol. 219 (9). Date of Electronic Publication: 2022 Aug 08.
DOI:	10.1084/jem.20212311
Abstrakt:	Enteric helminths form intimate physical connections with the intestinal epithelium, yet their ability to directly alter epithelial stem cell fate has not been resolved. Here we demonstrate that infection of mice with the parasite Heligmosomoides polygyrus bakeri (Hpb) reprograms the intestinal epithelium into a fetal-like state marked by the emergence of Clusterin-expressing revival stem cells (revSCs). Organoid-based studies using parasite-derived excretory-secretory products reveal that Hpb-mediated revSC generation occurs independently of host-derived immune signals and inhibits type 2 cytokine-driven differentiation of secretory epithelial lineages that promote their expulsion. Reciprocally, type 2 cytokine signals limit revSC differentiation and, consequently, Hpb fitness, indicating that helminths compete with their host for control of the intestinal stem cell compartment to promote continuation of their life cycle. (© 2022 Karo-Atar et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu