IL-12 and type I IFN response of neonatal myeloid DC to human CMV infection.
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.
Renneson
Joelle
J
Institute for Medical Immunology, Université Libre de Bruxelles, B-6041 Charleroi, Belgium.
Dutta
Binita
B
Goriely
Stanislas
S
Danis
Bénédicte
B
Lecomte
Sandra
S
Laes
Jean-François
JF
Tabi
Zsuzsanna
Z
Goldman
Michel
M
Marchant
Arnaud
A
D000328:Adult; D054370:Chemokine CXCL9 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D053765:Interleukin-12 Subunit p35 / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000378:metabolism; D000095022:Interferon Lambda
D054370:Chemokine CXCL9; D018925:Chemokines; D016207:Cytokines; D006680:HLA Antigens; D007370:Interferon Type I; D016898:Interferon-alpha; D016899:Interferon-beta; D007372:Interferons; D018664:Interleukin-12; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D007378:Interleukins; D014764:Viral Proteins; C080810:CXCL9 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda