Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology

Helen Mearns; William G C Horsnell; J Claire Hoving; Benjamin Dewals; Antony J Cutler; Frank Kirstein; Elmarie Myburgh; Berenice Arendse; Frank Brombacher

doi:10.1128/IAI.00210-08

Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology

Helen Mearns, William G C Horsnell, J Claire Hoving, Benjamin Dewals, Antony J Cutler, Frank Kirstein, Elmarie Myburgh, Berenice Arendse, Frank Brombacher

The Hull York Medical School

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

Abstract

The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T-cell IL-4Ralpha KO mice showed abrogation of airway mucus production. Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4, but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue-derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7 postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL-4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell populations and populations with CD4(+) T cells depleted showed that CD4(+) T cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte localization, and TH2 cytokine production in the allergic pathology associated with N. brasiliensis infections.

Original language	English
Pages (from-to)	5535-42
Number of pages	8
Journal	Infection and Immunity
Volume	76
Issue number	12
DOIs	https://doi.org/10.1128/IAI.00210-08
Publication status	Published - Dec 2008

Keywords

Animals
Chemotaxis, Leukocyte/immunology
Cytokines/biosynthesis
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunohistochemistry
Interleukin-4/deficiency
Lung/immunology
Mice
Mice, Knockout
Nippostrongylus/immunology
Strongylida Infections/immunology
Th2 Cells/immunology

Access to Document

10.1128/IAI.00210-08

Cite this

@article{0e975c248e2740ae8e5ac5adb213eaeb,

title = "Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology",

abstract = "The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T-cell IL-4Ralpha KO mice showed abrogation of airway mucus production. Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4, but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue-derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7 postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL-4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell populations and populations with CD4(+) T cells depleted showed that CD4(+) T cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte localization, and TH2 cytokine production in the allergic pathology associated with N. brasiliensis infections.",

keywords = "Animals, Chemotaxis, Leukocyte/immunology, Cytokines/biosynthesis, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunohistochemistry, Interleukin-4/deficiency, Lung/immunology, Mice, Mice, Knockout, Nippostrongylus/immunology, Strongylida Infections/immunology, Th2 Cells/immunology",

author = "Helen Mearns and Horsnell, {William G C} and Hoving, {J Claire} and Benjamin Dewals and Cutler, {Antony J} and Frank Kirstein and Elmarie Myburgh and Berenice Arendse and Frank Brombacher",

year = "2008",

month = dec,

doi = "10.1128/IAI.00210-08",

language = "English",

volume = "76",

pages = "5535--42",

journal = "Infection and Immunity",

issn = "1098-5522",

publisher = "American Society for Microbiology",

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T1 - Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology

AU - Mearns, Helen

AU - Horsnell, William G C

AU - Hoving, J Claire

AU - Dewals, Benjamin

AU - Cutler, Antony J

AU - Kirstein, Frank

AU - Myburgh, Elmarie

AU - Arendse, Berenice

AU - Brombacher, Frank

PY - 2008/12

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N2 - The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T-cell IL-4Ralpha KO mice showed abrogation of airway mucus production. Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4, but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue-derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7 postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL-4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell populations and populations with CD4(+) T cells depleted showed that CD4(+) T cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte localization, and TH2 cytokine production in the allergic pathology associated with N. brasiliensis infections.

AB - The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T-cell IL-4Ralpha KO mice showed abrogation of airway mucus production. Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4, but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue-derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7 postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL-4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell populations and populations with CD4(+) T cells depleted showed that CD4(+) T cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte localization, and TH2 cytokine production in the allergic pathology associated with N. brasiliensis infections.

KW - Animals

KW - Chemotaxis, Leukocyte/immunology

KW - Cytokines/biosynthesis

KW - Enzyme-Linked Immunosorbent Assay

KW - Flow Cytometry

KW - Immunohistochemistry

KW - Interleukin-4/deficiency

KW - Lung/immunology

KW - Mice

KW - Mice, Knockout

KW - Nippostrongylus/immunology

KW - Strongylida Infections/immunology

KW - Th2 Cells/immunology

U2 - 10.1128/IAI.00210-08

DO - 10.1128/IAI.00210-08

M3 - Article

C2 - 18809669

SN - 1098-5522

VL - 76

SP - 5535

EP - 5542

JO - Infection and Immunity

JF - Infection and Immunity

IS - 12

ER -