IFN-γ, IL-2, and IL-4 mRNA Expression in the Skin and Draining Lymph Nodes of BALB/c Mice Repeatedly Infested with Nymphal Ixodes ricinus Ticks

The skin and draining lymph nodes of BALB/c mice were examined for IFN-γ, IL-2, and IL-4 mRNA expression by in situ hybridization in three successive infestations with nymphal Ixodes ricinus ticks. IFN-γ and IL-2 mRNA positive cells were readily detected in lymph node sections during primary antigenic stimulation (72 hr post-tick attachment), whereas hybridization with IL-4 probe yielded no or only a faint positive signal. No changes in the cytokine pattern were observed in lymph node sections from reinfested mice, with IL-4 mRNA always being expressed to a lesser extent than IFN-γ and IL-2 mRNA. Seventy-two hours post-tick attachment in primary infestation, some infiltrating cells in the skin were positive for IFN-γ and IL-4 mRNA, but not for IL-2 mRNA. In skin sections of reinfested mice, mRNA coding for IFN-γ, IL-2, and IL-4 were detected in infiltrating cells. Cells positive for IL-4 mRNA were lower in number than those positive for IFN-γ and IL-2 mRNA. A significant decrease in the number of IL-4 mRNA positive cells in the tertiary infestation was noted. All together, these results indicate that I. ricinus nymphal ticks antigens are able to elicit expression of IFN-γ, IL-2 mRNA and to a lesser extent IL-4 mRNA in both skin and draining lymph nodes. In addition, repeated infestations with ticks led to strong expression of IFN-γ and IL-2 mRNAs in the skin that may be correlated with previous observations showing the occurrence of cutaneous delayed-type hypersensitivity in tick-infested mice. Notably, the cytokine pattern observed in the skin and draining lymph nodes is not associated with a protective immune response in mice against I. ricinus nymphal ticks infestations.