title: Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths.
abstract: Approximately one-third of the world population is infected with gastrointestinal helminths. Studies in mouse models have demonstrated that the cytokines interleukin (IL)-4 and IL-13 are essential for worm expulsion, but the critical cellular source of these cytokines is poorly defined. Here, we compared the immune response to Nippostrongylus brasiliensis in wild-type, T cell-specific IL-4/IL-13-deficient and general IL-4/IL-13-deficient mice. We show that T cell-derived IL-4/IL-13 promoted T helper 2 (Th2) polarization in a paracrine manner, differentiation of alternatively activated macrophages, and tissue recruitment of innate effector cells. However, innate IL-4/IL-13 played the critical role for induction of goblet cell hyperplasia and secretion of effector molecules like Mucin5ac and RELMβ in the small intestine. Surprisingly, T cell-specific IL-4/IL-13-deficient and wild-type mice cleared the parasite with comparable efficiency, whereas IL-4/IL-13-deficient mice showed impaired expulsion. These findings demonstrate that IL-4/IL-13 produced by cells of the innate immune system is required and sufficient to initiate effective type 2 immune responses resulting in protective immunity against N. brasiliensis.
authors.affiliation: Department of Infection Biology, Institute of Microbiology, Universitätsklinikum Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Oeser
authors.affiliation: Department of Infection Biology, Institute of Microbiology, Universitätsklinikum Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Department of Infection Biology, Institute of Microbiology, Universitätsklinikum Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Voehringer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000276:immunology / Q000469:parasitology; D006729:Hormones, Ectopic / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000235:genetics / Q000276:immunology; D009559:Nippostrongylus / Q000276:immunology*; D019899:Paracrine Communication; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology
chemical_list: D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D009077:Mucins; C486522:Retnlb protein, mouse; D015847:Interleukin-4