Natural measles causes prolonged suppression of interleukin-12 production.
Among vaccine-preventable diseases, measles is the preeminent killer of children worldwide. Infection with measles virus (MV) is associated with prolonged suppression of cell-mediated immune responses, a phenomenon that is thought to underlie the susceptibility to secondary infections that accounts for most measles-related mortality. Interleukin (IL)-12 is critical for the orchestration of cellular immunity. MV specifically ablates IL-12 production by monocyte/macrophages in vitro through binding to CD46, a complement regulatory protein that is an MV receptor. To address the effect of MV on IL-12 responses in vivo, cytokine production was examined in Gambian patients with measles. IL-12 production by peripheral blood monocytes from such patients is markedly suppressed, which provides a unifying mechanism for many of the immunologic abnormalities associated with measles. This suppression is prolonged, with significant, stimulus-specific inhibition of IL-12 production demonstrable months after recovery from acute infection. However, despite this suppression, IL-12 responsiveness remains intact.
Atabani
S F
SF
Medical Research Council Laboratories, Fajara, Banjul, The Gambia. atagp7@chmcc.gm
Byrnes
A A
AA
Jaye
A
A
Kidd
I M
IM
Magnusen
A F
AF
Whittle
H
H
Karp
C L
CL
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005714:Gambia; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008457:Measles / Q000276:immunology*; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; C497857:CD46 protein, human; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D018664:Interleukin-12; D007371:Interferon-gamma