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Updated: Jun 15, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Measles virus-induced immunosuppression in SLAM knock-in mice
Ritsuko Koga1, Shinji Ohno, Satoshi Ikegame
1Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Abstract:
Measles virus (MV) causes transient severe immunosuppression in patients, which may lead to secondary viral and bacterial infections, largely accounting for measles-related morbidity and mortality. MV is known to infect immune cells by using the human signaling lymphocyte activation molecule (SLAM; also called CD150) as a cellular receptor, but the mechanism by which MV causes immunosuppression is not well understood. We show that MV infection of SLAM knock-in mice, in which the V domain of mouse SLAM was replaced by the V domain of human SLAM, crossed with alpha/beta-interferon receptor knockout mice, reproduced many immunological alterations observed in human patients. These included lymphopenia, inhibition of T-cell proliferation and antibody production, increased production of the Th2 cytokine interleukin-4 (IL-4) and the immunosuppressive cytokine IL-10, and suppression of contact hypersensitivity. Gross redistribution of lymphocytes among lymphoid tissues was not apparent in infected mice, nor was an increase of regulatory T cells. The numbers of lymphocytes in lymph nodes remained almost unchanged after MV infection, despite enhanced apoptosis, suggesting that lymph nodes were replenished with lymphocytes from the peripheral blood, which may have contributed to the observed lymphopenia in the spleen. Blocking of IL-10 by use of an anti-IL-10 receptor antibody ameliorated suppression of contact hypersensitivity in infected mice. These results indicate that SLAM knock-in mice lacking the expression of the alpha/beta-interferon receptor serve as a useful small animal model with which to elucidate MV-induced immunosuppression.
Insights
Measles virus (MV) causes severe immunosuppression by infecting immune cells. A new mouse model reveals how MV impacts T-cells and antibody production, offering insights into measles pathogenesis.
Area of Science:
- Immunology
- Virology
- Pathogenesis
Background:
- Measles virus (MV) induces transient but severe immunosuppression, leading to secondary infections and mortality.
- The precise mechanisms underlying MV-induced immunosuppression remain incompletely understood.
- MV utilizes the signaling lymphocyte activation molecule (SLAM; CD150) as a cellular receptor for immune cell entry.
Purpose of the Study:
- To develop and validate a small animal model that recapitulates measles-induced immunosuppression observed in human patients.
- To investigate the immunological alterations caused by MV infection in a controlled experimental setting.
- To elucidate the specific pathways involved in MV-mediated suppression of immune responses.
Main Methods:
- Generation of SLAM knock-in mice with human SLAM V domain, crossed with alpha/beta-interferon receptor knockout mice.
- Infection of these genetically modified mice with Measles virus to study immunological changes.
- Analysis of lymphocyte populations, T-cell proliferation, antibody production, cytokine profiles (IL-4, IL-10), and contact hypersensitivity responses.
- Experimental blockade of interleukin-10 (IL-10) using an anti-IL-10 receptor antibody.
Main Results:
- The developed mouse model exhibited key immunological alterations seen in human measles patients, including lymphopenia and suppressed T-cell and antibody responses.
- Increased production of interleukin-4 (IL-4) and the immunosuppressive cytokine interleukin-10 (IL-10) was observed.
- Suppression of contact hypersensitivity was noted, and partially ameliorated by blocking IL-10.
- Lymphocyte redistribution was not a major factor; lymph node homeostasis appeared maintained despite peripheral apoptosis.
Conclusions:
- SLAM knock-in mice lacking the alpha/beta-interferon receptor provide a valuable model for studying measles virus-induced immunosuppression.
- Interleukin-10 plays a significant role in mediating the suppression of certain immune responses during measles infection.
- Further research using this model can elucidate the complex pathogenesis of measles and inform therapeutic strategies.
