Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox
Chaudhri, G and Panchanathan, V and Buller, RML and van den Eertwegh, AJM and Claassen, E and Zhou, J and de Chazal, R and Laman, JD and Karupiah, G, Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox, Proceedings of the National Academy of Sciences, 101, (24) pp. 9057-62. ISSN 0027-8424 (2004) [Refereed Article]
Ectromelia virus (ECTV), a natural mouse pathogen and an orthopoxvirus, has been used to investigate the correlation between
polarized type 1 or type 2 immune responses and resistance to
disease in poxvirus infections by using well defined resistant and
susceptible mouse strains. Our data show that distinct differences
exist in the cytokine profiles expressed in resistant and susceptible
mice infected with ECTV. Resistant C57BL6 mice generate a type
1 cytokine response [IFN-, IL-2, and tumor necrosis factor (TNF)],
within the first few days of infection, which is associated with
strong cytotoxic T lymphocyte response (CTL) and recovery from
ECTV infection. Susceptible strains of mice (BALBc and AJ) on the
other hand generate a type 2 cytokine response (IL-4 but little or
no IFN- and IL-2), which is associated with a weak or an absent CTL
response, resulting in uncontrolled virus replication and death.
Although deletion of IL-4 function alone did not change the
outcome of infection in susceptible mice, the loss of IFN- function
in resistant mice abrogated natural killer (NK) cell and CTL effector
functions resulting in fulminant disease and 100% mortality.
Therefore, a clear link exists between the early production of
specific type 1 cytokines, in particular, IFN-, the nature of the
cellular immune response, and disease outcome in this virus model.
This finding in the mousepox model raises the possibility that
inappropriate cytokine responses may result in increased susceptibility to smallpox in humans.
Th1 and Th2 cytokines; antiviral immunity; resistance to disease; poxvirus