Abstract
Following congenital human CMV (HCMV) infection, 15-20% of infected newborns develop severe health problems whereas infection in immunocompetent adults rarely causes illness. The immaturity of neonatal antigen presenting cells could play a pivotal role in this susceptibility. Neonatal myeloid DC were shown to be deficient in IFN-beta and IL-12 synthesis in response to TLR triggering. We studied the response of cord and adult blood-derived myeloid DC to HCMV infection. Neonatal and adult DC were equally susceptible to in vitro HCMV infection. Among immunomodulatory cytokines, IL-12, IFN-beta and IFN-lambda1 were produced at lower levels by neonatal as compared with adult DC. In contrast, neonatal and adult DC produced similar levels of IFN-alpha and IFN-inducible genes. Microarray analysis indicated that among the more than thousand genes up- or down-regulated by HCMV infection of myeloid DC, 88 were differently regulated between adult and neonatal DC. We conclude that neonatal and adult DC trigger a partly different response to HCMV infection. The deficient IL-12 and mature IFN-alpha production by neonatal DC exposed to HCMV are likely to influence the quality of the T lymphocyte response to HCMV infection in early life.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Chemokine CXCL9 / metabolism
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Chemokines / genetics
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Chemokines / metabolism
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Cytokines / genetics
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Cytokines / metabolism
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Cytomegalovirus / immunology*
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Cytomegalovirus / metabolism
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / virology*
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Down-Regulation / genetics
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Down-Regulation / immunology
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Gene Expression / genetics
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Gene Expression / immunology
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Gene Expression Profiling
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HLA Antigens / metabolism
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Humans
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Infant, Newborn
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Interferon Type I / genetics
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Interferon Type I / immunology*
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Interferon-alpha / genetics
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Interferon-alpha / metabolism
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Interferon-beta / genetics
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Interferon-beta / metabolism
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Interferons / genetics
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Interferons / metabolism
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Interleukin-12 / genetics
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Interleukin-12 / immunology*
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Interleukin-12 Subunit p35 / genetics
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Interleukin-12 Subunit p35 / metabolism
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Interleukin-12 Subunit p40 / genetics
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Interleukin-12 Subunit p40 / metabolism
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Interleukins / metabolism
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Oligonucleotide Array Sequence Analysis
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Up-Regulation / genetics
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Up-Regulation / immunology
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Viral Proteins / metabolism
Substances
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CXCL9 protein, human
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Chemokine CXCL9
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Chemokines
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Cytokines
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HLA Antigens
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interferon-lambda, human
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Interferon Type I
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Interferon-alpha
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Interleukin-12 Subunit p35
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Interleukin-12 Subunit p40
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Interleukins
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Viral Proteins
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Interleukin-12
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Interferon-beta
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Interferons