title: IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections.
abstract: Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong T(H)2 polarization of the host's immune response. We present data demonstrating N. brasiliensis-driven airway mucus production to be dependent on smooth muscle cell interleukin 4 receptor-α (IL-4Rα) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4Rα(-/lox) control mice, whereas global knockout (IL-4Rα(-/-)) and smooth muscle-specific IL-4Rα-deficient mice (SM-MHC(Cre) IL-4Rα(-/lox)) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC(Cre) IL-4Rα(-/lox) mice was impaired along with a transient reduction in T-cell numbers in the lung. In vitro treatment of smooth muscle cells with secreted N. brasiliensis excretory-secretory antigen (NES) induced IL-6 production. Decreased protein kinase C (PKC)-dependent smooth muscle cell proliferation associated with cell cycle arrest was found in cells stimulated with NES. Together, these data demonstrate that both IL-4Rα and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections.
authors.affiliation: Division of Immunology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: W G C
authors.initials: WG
authors.lastname: Horsnell
authors.forename: A
authors.initials: A
authors.lastname: Vira
authors.forename: F
authors.initials: F
authors.lastname: Kirstein
authors.forename: H
authors.initials: H
authors.lastname: Mearns
authors.forename: J C
authors.initials: JC
authors.lastname: Hoving
authors.forename: A J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: B
authors.initials: B
authors.lastname: Dewals
authors.forename: E
authors.initials: E
authors.lastname: Myburgh
authors.forename: M
authors.initials: M
authors.lastname: Kimberg
authors.forename: B
authors.initials: B
authors.lastname: Arendse
authors.forename: N
authors.initials: N
authors.lastname: White
authors.forename: A
authors.initials: A
authors.lastname: Lopata
authors.forename: P E
authors.initials: PE
authors.lastname: Burger
authors.forename: F
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D005434:Flow Cytometry; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008174:Lung Diseases, Parasitic / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000276:immunology* / Q000378:metabolism*; D009559:Nippostrongylus / Q000276:immunology* / Q000472:pathogenicity; D011493:Protein Kinase C / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D015848:Interleukin-5; D015850:Interleukin-6; D011493:Protein Kinase C