Type 1 and type 2 cytokines in antiviral defense

Abstract

Ectromelia virus (EV) is a natural mouse pathogen that causes a generalized infection termed mousepox, which, in the genetically resistant C57BL/6 (B6) mouse, is an inapparent disease. In contrast, BALB/c and A strain mice are highly susceptible; one infectious virus particle can result in 100% mortality. The contribution of cytokines in the induction of protective immune responses and recovery from infection with EV in B6, BALB/c and A strain mice have been. In the spleen and lymph node (LN) of resistant B6 mice, IL-2, IFN-gamma and TNF-alpha were induced rapidly with large numbers of cells producing these cytokines. All three cytokines were virtually absent in BALB/c and A strain mice. No significant differences were found in the numbers of IL-4 producing cells in the spleen or LN of both resistant and susceptible mice. IFN-gamma-producing cells were detected in the spleen but not in the lymph node whereas IL-2-producing cells were detected only in the lymph node of B6 mice. Despite significant increases in the IFN-gamma mRNA levels in the LN of B6 mice, no protein was detected by immunocytochemistry. The mRNA levels of IL-2, TNF-alpha and IL-12 were also rapidly upregulated in LN of B6 mice. The rapid induction of type I cytokines strongly correlated with a potent antiviral CTL response in B6 mice. The absence of these cytokines also correlated with a complete absence or delayed induction of CTL responses to EV in both the BALB/c and A strain mice. IFN-gamma gene knock out mice on a B6 background were as susceptible to EV as the BALB/c and A strain mice.