Distinct immune responses in resistant and susceptible strains of mice during neurovirulent alphavirus encephalomyelitis.

Kulcsar KA, Baxter VK, Abraham R, Nelson A, Griffin DE.

Citation

Kulcsar KA, Baxter VK, Abraham R, Nelson A, Griffin DE. (2015) Distinct immune responses in resistant and susceptible strains of mice during neurovirulent alphavirus encephalomyelitis. Journal of Virology 89(16):8280-8291.

Abstract

Mosquito-borne alphavirus infections are an important cause of encephalomyelitis in humans. The severity of disease is dependent both on the strain of the virus and on the age and genetic background of the host. A neurovirulent strain of Sindbis virus causes immune-mediated fatal encephalomyelitis in adult C57BL/6 mice but not in BALB/c mice. To determine the host-dependent immunological mechanisms underlying the differences in susceptibility between these two strains of mice, we compared their immune responses to infection. Resistance to fatal disease in BALB/c mice was associated with better antibody responses, more-rapid virus clearance, fewer Th17 cells, and more-potent regulatory T cell responses than occurred in susceptible C57BL/6 mice. In the absence of interleukin-10, a component of the regulatory immune response, resistant mice became susceptible to lethal disease. This study demonstrates the importance of the immune response and its regulation for host survival during alphavirus encephalomyelitis.