Children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable Haemophilus influenzae

PLoS One. 2014 Aug 11;9(8):e104236. doi: 10.1371/journal.pone.0104236. eCollection 2014.

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-γ, IL-13, IL-5, IL-10 at 72 hours and TNFα, 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-γ in response to NTHi than healthy control children whereas mitogen-induced IFN-γ 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-γ response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibody Specificity
  • Child
  • Chronic Disease
  • Disease Susceptibility
  • Female
  • Haemophilus influenzae / immunology
  • Haemophilus influenzae / physiology*
  • Humans
  • Immunity, Innate
  • Infant
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / metabolism
  • Lung Diseases / blood
  • Lung Diseases / immunology
  • Lung Diseases / metabolism*
  • Lung Diseases / microbiology*
  • Male

Substances

  • Antibodies, Bacterial
  • Interferon-gamma

Grant support

SP is funded by an Australian National Health and Medical Research Council postgraduate scholarship (1038415); AC (grant 545216) and JU (grant 511019) funded by Australian National Health and Medical Research Council practitioner fellowships (https://www.nhmrc.gov.au). The study was funded by Channel 7 Children's Research Foundation (grant 13688; http://www.crf.org.au) and supported by Australian National Health and Medical Research Council Center for Research Excellence for Lung Health of Aboriginal and Torres Strait Islander (grant 1040830). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.