Expression of the natural resistance gene Lsh in resident liver macrophages

Abstract

Innate resistance and susceptibility to Leishmania donovani infection in mice is controlled by a single gene (Lsh) thought to be identical to the genes Ity and Bcg which control the early response to Salmonella typhimurium and Mycobacterium bovis infections, respectively. In the present study, three new aspects of Lsh gene activity were demonstrated. First, it was shown that liver macrophages continue to express Lsh gene activity in vitro after their extraction from mice infected in vivo, although 2 days of infection were required before the resistant phenotype was expressed. Second, detailed examination of early growth of the parasite and tritiated thymidine labeling of the parasites indicated that this delay in expression of the resistant phenotype also occurred in vivo. Third, the expression of resistance was unaltered by the effects of lethal irradiation but could be selectively enhanced by prior treatment with suitable doses of S. typhimurium lipopolysaccharide or L. donovani membranes. These results suggest that the resistance mechanism may be expressed by resident liver macrophages after their interaction with parasite-derived material. The relevance of these findings to the other intramacrophage pathogens is discussed.