Children with Chronic Suppurative Lung Disease Have a Reduced Capacity to Synthesize Interferon-Gamma In Vitro in Response to Non-Typeable Haemophilus influenzae

Susan Pizzutto, Stephanie Yerkovich, John Upham, Belinda Hales, Wayne Thomas, Anne Chang

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    Abstract

    Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-?, IL-13, IL-5, IL-10 at 72 hours and TNF?, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-c in response to NTHi than healthy control children whereas mitogen-induced IFN-? production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-? response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.
    Original languageEnglish
    Article numbere104236
    Pages (from-to)1-10
    Number of pages10
    JournalPLoS One
    Volume9
    Issue number8
    DOIs
    Publication statusPublished - 11 Aug 2014

    Fingerprint

    Haemophilus influenzae
    Pulmonary diseases
    interferon-gamma
    respiratory tract diseases
    Lung Diseases
    Interferon-gamma
    Immunoglobulin G
    Humoral Immunity
    mononuclear leukocytes
    interleukin-10
    humoral immunity
    Respiratory Tract Infections
    cell-mediated immunity
    Interleukin-10
    Haemophilus Infections
    infection
    interleukin-5
    Interleukin-13
    cough
    In Vitro Techniques

    Cite this

    Pizzutto, Susan ; Yerkovich, Stephanie ; Upham, John ; Hales, Belinda ; Thomas, Wayne ; Chang, Anne. / Children with Chronic Suppurative Lung Disease Have a Reduced Capacity to Synthesize Interferon-Gamma In Vitro in Response to Non-Typeable Haemophilus influenzae. In: PLoS One. 2014 ; Vol. 9, No. 8. pp. 1-10.
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    abstract = "Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-?, IL-13, IL-5, IL-10 at 72 hours and TNF?, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-c in response to NTHi than healthy control children whereas mitogen-induced IFN-? production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-? response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.",
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    author = "Susan Pizzutto and Stephanie Yerkovich and John Upham and Belinda Hales and Wayne Thomas and Anne Chang",
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    Children with Chronic Suppurative Lung Disease Have a Reduced Capacity to Synthesize Interferon-Gamma In Vitro in Response to Non-Typeable Haemophilus influenzae. / Pizzutto, Susan; Yerkovich, Stephanie; Upham, John; Hales, Belinda; Thomas, Wayne; Chang, Anne.

    In: PLoS One, Vol. 9, No. 8, e104236, 11.08.2014, p. 1-10.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Children with Chronic Suppurative Lung Disease Have a Reduced Capacity to Synthesize Interferon-Gamma In Vitro in Response to Non-Typeable Haemophilus influenzae

    AU - Pizzutto, Susan

    AU - Yerkovich, Stephanie

    AU - Upham, John

    AU - Hales, Belinda

    AU - Thomas, Wayne

    AU - Chang, Anne

    N1 - NHMRC Grant No.: 1038415

    PY - 2014/8/11

    Y1 - 2014/8/11

    N2 - Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-?, IL-13, IL-5, IL-10 at 72 hours and TNF?, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-c in response to NTHi than healthy control children whereas mitogen-induced IFN-? production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-? response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.

    AB - Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-?, IL-13, IL-5, IL-10 at 72 hours and TNF?, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-c in response to NTHi than healthy control children whereas mitogen-induced IFN-? production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-? response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.

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    KW - interleukin 6

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    KW - Klebsiella pneumoniae

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    KW - Moraxella catarrhalis

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    KW - preschool child

    KW - Pseudomonas aeruginosa

    KW - school child

    KW - Streptococcus pneumoniae

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    KW - physiology

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