[en] Although widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner. Deletion of Chat within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection. Our results reveal a genetic proof of function for ChAT in T cells during viral infection and identify a pathway of T cell migration that sustains antiviral immunity.
Disciplines :
Immunology & infectious disease
Author, co-author :
Cox, Maureen A ; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Duncan, Gordon S; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Lin, Gloria H Y; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Steinberg, Benjamin E; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada ; Department of Anesthesia, University of Toronto, Toronto, ON M5G 1E2, Canada
Yu, Lisa X; Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5T 3H7, Canada
BRENNER, Dirk ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics ; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada ; Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-sur-Alzette, Luxembourg ; Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark
Buckler, Luke N; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Elia, Andrew J ; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Wakeham, Andrew C; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Nieman, Brian; Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5T 3H7, Canada ; Ontario Institute for Cancer Research and Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2C1, Canada
Dominguez-Brauer, Carmen; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Elford, Alisha R; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Gill, Kyle T ; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Kubli, Shawn P; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Haight, Jillian ; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Berger, Thorsten; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
Ohashi, Pamela S; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada ; Department of Immunology, University of Toronto, Toronto, ON M5G 2C1, Canada
Tracey, Kevin J ; Laboratory of Biomedical Science, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA
Olofsson, Peder S ; Laboratory of Biomedical Science, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA ; Center for Bioelectronic Medicine, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden
Mak, Tak W ; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. tmak@uhnresearch.ca ; Ontario Institute for Cancer Research and Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2C1, Canada ; Department of Immunology, University of Toronto, Toronto, ON M5G 2C1, Canada ; Department of Pathology, University of Hong Kong, Hong Kong
This work was supported by the Cancer Research Institute Irvington Postdoctoral Fellowship (to M.A.C.), the Knut and Alice Wallenberg Foundation (P.S.O.), and grants from the Canadian Institutes of Health Research (to T.W.M.). D.B. is supported by the FNR-ATTRACT (A14/BM/7632103).
