title: Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection.
abstract: Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) beta. RELM-beta is essential for normal spontaneous expulsion and IL-4-induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-beta is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-beta-driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.
authors.affiliation: Research Service, Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220, USA.
authors.forename: De'Broski R
authors.initials: DR
authors.lastname: Herbert
authors.forename: Jun-Qi
authors.initials: JQ
authors.lastname: Yang
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hogan
authors.forename: Kathryn
authors.initials: K
authors.lastname: Groschwitz
authors.forename: Marat
authors.initials: M
authors.lastname: Khodoun
authors.forename: Ariel
authors.initials: A
authors.lastname: Munitz
authors.forename: Tatyana
authors.initials: T
authors.lastname: Orekov
authors.forename: Charles
authors.initials: C
authors.lastname: Perkins
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
mesh_terms: D000818:Animals; D041981:Gastrointestinal Tract / Q000469:parasitology*; D006729:Hormones, Ectopic / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology*; D009559:Nippostrongylus / Q000276:immunology*
chemical_list: D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; C486522:Retnlb protein, mouse; D015847:Interleukin-4