RESPONSE OF SCID MICE TO ESTABLISHMENT OF LEISHMANIA-MAJOR INFECTION

The initiation of Leishmania major infection in susceptible BALB/c mic e is regulated by interferon-gamma (IFN-gamma). To examine further the mechanisms of IFN-gamma-dependent regulation of the establishment of L. major, we studied the characteristics of the infection in severe co mbined immunodeficient (scid) mice. In the first 2 weeks of infection, we observed a delay in the development of the lesions in the footpads and lower numbers of parasites in scid compared with BALB/c mice, By week 5 after infection, the size of the leishmanial lesion was similar in both strains of mice, but the number of parasites in scid mice was 100-fold higher than in BALB/c. Treatment with anti-IFN-gamma during the establishment of L. major did not alter the course of infection in scid mice, while it exacerbated lesion development in BALB/c mice. Ma crophages from scid mice were unable to kill L. major when stimulated with IFN-gamma in vitro, and produced lower levels of nitric oxide com pared with macrophages from susceptible BALB/c or the resistant C57B1/ 6 mice. We examined whether delayed lesion development in scid mice wa s due to their inability to mount appropriate inflammatory responses. While significantly fewer nucleated cells were present in the footpads of scid mice compared with BALB/c, 2 and 3 weeks after infection, no difference in inflammatory response between scid and BALB/c mice was o bserved in response to L. major antigen in the footpads. In contrast, there was a dramatic increase in the number of cells in the popliteal lymph nodes of BALB/c mice. Decreased inflammatory responses of scid m ice in the footpad (at the site of infection) may contribute to slower development of leishmanial lesions during the first 2 weeks of infect ion.