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Natural measles causes prolonged suppression of interleukin-12 production
S F Atabani1, A A Byrnes, A Jaye
1Medical Research Council Laboratories, Fajara, Banjul, The Gambia. atagp7@chmcc.gm
Abstract:
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.
Insights
Measles virus (MV) infection suppresses interleukin-12 (IL-12) production in children, increasing susceptibility to deadly secondary infections. This immune suppression persists long after recovery, impacting cellular immunity.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Measles is a leading cause of child mortality globally.
- Measles virus (MV) infection causes immune suppression, leading to secondary infections and mortality.
- Interleukin-12 (IL-12) is crucial for cell-mediated immunity.
Purpose of the Study:
- To investigate the in vivo effect of measles virus on interleukin-12 (IL-12) production.
- To understand the immunologic basis of measles-related mortality.
Main Methods:
- Examined cytokine production in Gambian children with measles.
- Measured IL-12 production by peripheral blood monocytes.
Main Results:
- Measles virus infection markedly suppresses IL-12 production in peripheral blood monocytes.
- This IL-12 suppression is prolonged, persisting for months after acute infection recovery.
- IL-12 responsiveness remains intact despite suppressed production.
Conclusions:
- Measles virus-induced IL-12 suppression provides a unifying mechanism for measles-associated immunologic abnormalities.
- The prolonged suppression of IL-12 contributes to increased susceptibility to secondary infections.
- Understanding this mechanism is critical for addressing measles-related mortality.