Suppression of innate immune cytokines and interferon regulatory factor-1 by endogenous interferon-alpha in response to respiratory syncytial virus in neonate mononuclear cells.
Respiratory syncytial virus (RSV) infections are extremely common in early childhood but are most severe in infants in the first few months of life. Unresponsive adaptive immunity and hyporesponsive innate immunity were previously found to be the typical responses of neonate mononuclear cells (MCs) to live RSV. Investigating the mechanism of innate immune hyporesponsiveness in neonate MCs to live RSV revealed that in contrast to the previously reported low expression of interferon (IFN)-gamma, IFN-alpha expression in response to live RSV was significantly greater than that observed in adult MCs. Inhibition of live RSV-induced IFN-alpha with anti-IFN-alpha antibodies in neonate MCs led to significant increases in innate cytokine [IFN-gamma, interleukin (IL)-12, IL-18 and tumor necrosis factor (TNF)-alpha] but not adaptive immune cytokine [IL-2] production. Although MCs from adults responded to live RSV with upregulation of interferon regulatory factor-1 (IRF-1) mRNA, IRF-1 mRNA in RSV-treated neonate MCs was not detectable. However, in the presence of anti-IFN-alpha antibodies, live RSV induced detectable IRF-1 mRNA expression in neonate MCs. These data support the possibility that the severity of early life RSV-induced illnesses may occur via a mechanism in which live RSV induces IFN-alpha that in turn leads to innate immune suppression in neonate MCs.
Krishnan
Subramaniam
S
Graduate Program in Microbiology and Immunology, University of Arizona HSC, Tucson, Arizona 85724, USA.
Halonen
Marilyn
M
D000328:Adult; D016207:Cytokines; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D050856:Interferon Regulatory Factor-1 / Q000276:immunology* / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha