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IL-12 and type I IFN response of neonatal myeloid DC to human CMV infection

Joelle Renneson1, Binita Dutta, Stanislas Goriely

  • 1Institute for Medical Immunology, Université Libre de Bruxelles, B-6041 Charleroi, Belgium.

European Journal of Immunology
|July 29, 2009
PubMed

Insights

Neonatal myeloid dendritic cells (DC) show a weaker immune response to human cytomegalovirus (HCMV) infection compared to adults. This deficiency in cytokine production may impact T cell responses in newborns.

Area of Science:

  • Immunology
  • Virology
  • Neonatal Health

Background:

  • Congenital human cytomegalovirus (HCMV) infection causes severe health issues in 15-20% of newborns, unlike in immunocompetent adults.
  • Immature neonatal antigen-presenting cells are suspected to contribute to this susceptibility.
  • Neonatal myeloid dendritic cells (DC) exhibit deficiencies in IFN-beta and IL-12 synthesis upon Toll-like receptor (TLR) triggering.

Purpose of the Study:

  • To investigate and compare the response of neonatal and adult myeloid DC to HCMV infection.
  • To identify differences in cytokine production and gene regulation between neonatal and adult myeloid DC upon HCMV exposure.

Main Methods:

  • Cultured myeloid DC derived from both cord (neonatal) and adult blood.
  • In vitro infection of DC with HCMV.
  • Quantification of immunomodulatory cytokines (IL-12, IFN-beta, IFN-lambda1, IFN-alpha).
  • Microarray analysis to assess gene expression changes.

Main Results:

  • Neonatal and adult myeloid DC demonstrated equal susceptibility to in vitro HCMV infection.
  • Neonatal DC produced significantly lower levels of IL-12, IFN-beta, and IFN-lambda1 compared to adult DC.
  • IFN-alpha and IFN-inducible gene production were similar in both neonatal and adult DC.
  • Microarray analysis revealed 88 genes with differential regulation between adult and neonatal DC following HCMV infection.

Conclusions:

  • Neonatal and adult myeloid DC mount partly distinct responses to HCMV infection.
  • Deficient IL-12 and mature IFN-alpha production by neonatal DC may impair the quality of T lymphocyte responses to HCMV in early life.

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