Targeting acetylcholine receptors to enhance immunity to infection

LE STUDIUM Multidisciplinary Journal, 2018, 2, 78-88

Luke B. Roberts1, Corinna Schnoeller1, Matthew Darby2, Claire Mackowiak3, Delphine Sedda3, Valerie Quesniaux3, Bernhard Ryffel3, Rachel Vaux1, Rita Berkachy1, Kleoniki Gounaris1, William G. C. Horsnell2,3,4, and Murray E. Selkirk1

 

1 Department of Life Sciences, Imperial College London, London, UK

2 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

3 Laboratory of Molecular and Experimental Immunology and Neurogenetics, UMR 7355, CNRS-University of Orleans and Le Studium Institute for Advanced Studies, Rue Dupanloup, 45000 Orléans, France.

4 Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

Abstract

Group 2 innate lymphoid cell (ILC2s) responses drive type 2 immunity against helminths and are initiated by host alarmin release. Here we show that in addition to signature type 2 cytokines ILC2 also synthesise and release acetylcholine (ACh).  ILC2 ACh synthesis (defined by choline acetyltransferase (ChAT) expression) following Nb or Alternaria challenge revealed pronounced ACh synthesis in ILC2 when compared to other immune cell populations. In vivo alarmin cytokine challenges selectively induced this ILC2 ACh responses. Nippostrongylus brasiliensis infection of RORCreChATLoxP mice (which have a targeted disruption of the ILC2 ACh response) resulted in higher intestinal helminth burdens than in control mice.  This impaired control of infection associated with reduced ILC2 and CD4 IL-13 production. Adoptive transfer of  RORCreChATLoxP ILC2s into RAG2-/-IL-2rg-/- resulted in subsequent infection having a higher intestinal burden than in ChATloxp recipeints. These data identify ILC2-derived ACh as a novel axis required for optimal type 2 immunity.

 

Keywords

Immunology
acetylcholine
lung inflammation
innate immunity
virus
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LE STUDIUM Multidisciplinary Journal