Gamma interferon is not required for arthritis resistance in the murine lyme disease model

Lyme arthritis is the most common complication following infection of human individuals with Borrelia burgdorferi sensu stricto. In mice, B. burgdorfe ri infection leads to arthritis of the tibiotarsal joints. Arthritis severi ty in mice is under host genetic control, as BALB/c mice developed mild art hritis but C3H/He mice developed severe disease following B. burgdorferi in fection. To study the role of gamma interferon (IFN-gamma) in arthritogenes is, targeted mutant mice lacking the IFN-gamma receptor (IFN-gammaR) were i nfected by inoculation with B. burgdorferi. IFN-gammaR(-/-) and parental 12 9/SvEv mice developed mild arthritis of similar severity, as determined bot h by weekly tibiotarsal joint measurements and histopathology at 2 and 5 we eks postinfection, Both strains of mice had the same spirochetal burden in the joints, suggesting that the IFN-gammaR(-/-) mice were not impaired in c ontrolling spirochetal expansion in vivo. The wild-type mice mounted a Th1 response, with a predominance of CD4(+) IFN-gamma (+) T cells observed by f low cytometry. In contrast, the IFN-gammaR(-/-) mice mounted a Th2 response , with a predominance of CD4(+) IL-4(+) T cells. As expected given their cy tokine profile, the IFN-gammaR(-/-) mice produced fewer CD8(+) IFN-gamma () and MAC-1(+) IL-12(+) cells and less immunoglobulin G2a (IgG2a) than thei r wild-type counterparts. These results strongly suggest that IFN-gamma is not required for arthritis resistance or as part of an effective immune res ponse against B. burgdorferi.