Targeting acetylcholine receptors to enhance immunity to infection

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^CreChAT^LoxP 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^CreChAT^LoxP ILC2s into RAG2^-/-IL-2rg^-/- resulted in subsequent infection having a higher intestinal burden than in ChAT^loxp recipeints. These data identify ILC2-derived ACh as a novel axis required for optimal type 2 immunity.