IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

W G C Horsnell; A Vira; F Kirstein; H Mearns; J C Hoving; A J Cutler; B Dewals; E Myburgh; M Kimberg; B Arendse; N White; A Lopata; P E Burger; Frank Brombacher

doi:10.1038/mi.2010.46

IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

W G C Horsnell, A Vira, F Kirstein, H Mearns, J C Hoving, A J Cutler, B Dewals, E Myburgh, M Kimberg, B Arendse, N White, A Lopata, P E Burger, Frank Brombacher

The Hull York Medical School

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	83-92
Number of pages	10
Journal	Mucosal Immunology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/mi.2010.46
Publication status	Published - Jan 2011

Keywords

Animals
Cell Cycle/genetics
Flow Cytometry
Interleukin-13/biosynthesis
Interleukin-4 Receptor alpha Subunit/genetics
Interleukin-5/biosynthesis
Interleukin-6/biosynthesis
Lung Diseases, Parasitic/immunology
Mice
Mice, Inbred BALB C
Mice, Knockout
Mucus/metabolism
Myocytes, Smooth Muscle/immunology
Nippostrongylus/immunology
Protein Kinase C/metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Strongylida Infections/immunology
Th2 Cells/immunology

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10.1038/mi.2010.46

Cite this

Horsnell, W. G. C., Vira, A., Kirstein, F., Mearns, H., Hoving, J. C., Cutler, A. J., Dewals, B., Myburgh, E., Kimberg, M., Arendse, B., White, N., Lopata, A., Burger, P. E., & Brombacher, F. (2011). IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunology, 4(1), 83-92. https://doi.org/10.1038/mi.2010.46

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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.",

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author = "Horsnell, {W G C} and A Vira and F Kirstein and H Mearns and Hoving, {J C} and Cutler, {A J} and B Dewals and E Myburgh and M Kimberg and B Arendse and N White and A Lopata and Burger, {P E} and Frank Brombacher",

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Horsnell, WGC, Vira, A, Kirstein, F, Mearns, H, Hoving, JC, Cutler, AJ, Dewals, B, Myburgh, E, Kimberg, M, Arendse, B, White, N, Lopata, A, Burger, PE & Brombacher, F 2011, 'IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections', Mucosal Immunology, vol. 4, no. 1, pp. 83-92. https://doi.org/10.1038/mi.2010.46

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T1 - IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

AU - Horsnell, W G C

AU - Vira, A

AU - Kirstein, F

AU - Mearns, H

AU - Hoving, J C

AU - Cutler, A J

AU - Dewals, B

AU - Myburgh, E

AU - Kimberg, M

AU - Arendse, B

AU - White, N

AU - Lopata, A

AU - Burger, P E

AU - Brombacher, Frank

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N2 - 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.

AB - 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.

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KW - Cell Cycle/genetics

KW - Flow Cytometry

KW - Interleukin-13/biosynthesis

KW - Interleukin-4 Receptor alpha Subunit/genetics

KW - Interleukin-5/biosynthesis

KW - Interleukin-6/biosynthesis

KW - Lung Diseases, Parasitic/immunology

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Knockout

KW - Mucus/metabolism

KW - Myocytes, Smooth Muscle/immunology

KW - Nippostrongylus/immunology

KW - Protein Kinase C/metabolism

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Strongylida Infections/immunology

KW - Th2 Cells/immunology

U2 - 10.1038/mi.2010.46

DO - 10.1038/mi.2010.46

M3 - Article

C2 - 20737001

SN - 1933-0219

VL - 4

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EP - 92

JO - Mucosal Immunology

JF - Mucosal Immunology

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