EFFECTS OF IXODES-SCAPULARIS AND BORRELIA-BURGDORFERI ON MODULATION OF THE HOST IMMUNE-RESPONSE - INDUCTION OF A TH2 CYTOKINE RESPONSE IN LYME-DISEASE-SUSCEPTIBLE (C3H HEJ) MICE BUT NOT IN DISEASE-RESISTANT (BALB/C) MICE/

Previous studies have demonstrated that both Ixodes scapularis saliva and Borrelia burgdorferi antigens modulated lymphokines and monokines in vitro, The studies presented here were designed to delineate the ro le of I. scapularis and B, burgdorferi in modulation of the host immun e response in vivo, Infestation of C3H/HeJ mice with infected I. scapu laris resulted in an up regulation of IL-4 as early as 8 days after ti ck infestation, while the levels of T helper cell type 1 (TH1) cytokin es, interleukin-2 (IL-2) and gamma interferon (IFN-gamma), were signif icantly decreased by days 10 to 12. In contrast, the cytokine profile of BALB/c mice exposed to infected nymphal ticks resulted in only tran sient alterations in IL-4, IL-2, and IFN-gamma production throughout a 12-day period postinfestation. Although the IL-10 level was elevated in both C3H/HeJ and BALB/c mice infested with infected nymphal ticks, no significant difference in the levels of IL-10 was noted between the mouse strains. Flow-cytometric analysis demonstrated increases in the numbers of splenic B-cell and CD4(+) lymphocytes in C3H/HeJ but not B ALB/c mice exposed to infected ticks. Cell depletion experiments with C3H/HeJ mice demonstrated that CD4(+) cells were the sole producers of IFN-gamma, and IL-10 while both CD4(+) and CD8(+) splenocytes contrib uted to the production of IL-2 and IL-4, These findings suggest that B and CD4(+) splenocytes are activated, increase in number, and produce a polarized TH2 response in C3H/HeJ mice exposed to infected I. scapu laris, Given that C3H/HeJ mice are susceptible to Lyme disease and the initial TH2 polarization is not evident in BALB/c mice, effective con trol of this response may have ramifications for spirochete transmissi on in vivo.