title: 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.
authors.affiliation: Department of Medicine, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: Nirav
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Medicine, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Medicine, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Mishra
authors.affiliation: Department of Medicine, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Medicine, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Millman
authors.affiliation: Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Department of Surgery, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: Balázs
authors.initials: B
authors.lastname: Csóka
authors.affiliation: Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Department of Surgery, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: Balázs
authors.initials: B
authors.lastname: Koscsó
authors.affiliation: Department of Anesthesiology, Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
authors.affiliation: Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Department of Surgery, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: György
authors.initials: G
authors.lastname: Haskó
authors.affiliation: Department of Medicine, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07101, USA. Electronic address: gausewc@umdnj.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Gause
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009348:Nematoda / Q000276:immunology*; D009351:Nematospiroides dubius / Q000276:immunology*; D043704:Receptor, Adenosine A2B / Q000172:deficiency / Q000378:metabolism*; D017206:Strongylida Infections / Q000276:immunology*
chemical_list: D016207:Cytokines; D043704:Receptor, Adenosine A2B; D000241:Adenosine