Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection.
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.
Herbert
De'Broski R
DR
Research Service, Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220, USA.
Yang
Jun-Qi
JQ
Hogan
Simon P
SP
Groschwitz
Kathryn
K
Khodoun
Marat
M
Munitz
Ariel
A
Orekov
Tatyana
T
Perkins
Charles
C
Wang
Quan
Q
Brombacher
Frank
F
Urban
Joseph F
JF
Rothenberg
Marc E
ME
Finkelman
Fred D
FD
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*
D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; C486522:Retnlb protein, mouse; D015847:Interleukin-4