A2B adenosine receptor induces protective antihelminth type 2 immune responses.

Abstract:

:The type 2 immune response evoked by intestinal nematode parasites contributes to worm expulsion and tolerance to associated tissue damage. We investigated whether this host response is affected by blocking signaling by the putative endogenous danger signal adenosine, which can be released during inflammation and host cell damage. Specific blockade of the A2B adenosine receptor (A2BAR) inhibited worm elimination and the development of innate and adaptive components of the type 2 primary and memory response. Infected mice lacking A2BAR exhibited decreased M2 macrophage and eosinophil recruitment and reduced IL-4 and IL-13 cytokine production. Additionally, shortly after infection, upregulation of the alarmin IL-33, which drives type 2 immunity, and activation of innate lymphoid type 2 (ILC2) cells was inhibited, while exogenous IL-33 restored ILC2 cell activation and type 2 cytokine expression. Thus, adenosine acts as a danger-associated molecular pattern (DAMP) that initiates helminth-induced type 2 immune responses through A2BAR.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Patel N,Wu W,Mishra PK,Chen F,Millman A,Csóka B,Koscsó B,Eltzschig HK,Haskó G,Gause WC

doi

10.1016/j.chom.2014.02.001

subject

Has Abstract

pub_date

2014-03-12 00:00:00

pages

339-50

issue

3

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(14)00059-6

journal_volume

15

pub_type

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