Immunological regulation of experimental cutaneous leishmaniasis. 1. Immunogenetic aspects of susceptibility to Leishmania tvopica in mice

Abstract

Models of the different disease patterns of cutaneous leishmaniasis can be induced by the same dose of L. tropica promastigotes in various inbred strains of mice. The susceptibility of BALB/c is exceptional, essentially dosage independent (being demonstrable with as few as 20 parasites) and leads to huge progressive lesions with fetal visceral and cutaneous metastasis. Lesions also extend progressively but more slowly in DBA/1 and DBA/2 mice. Strains A, C57BL/6 and CBA are relatively resistant to even 2 .times. 107 promastigotes, with arrest of lesion growth within 3 wk and subsequent gradual healing. Similar resistance of A.SW to 2 .times. 105 is overcome by a larger dose. The major inter-strain differences are H-2 independent, for C57BL/10 congenic mice possessing 6 different H-2 antigen complexes all show early arrest of lesion growth leading to healing (H-2s, H-2a, H-2k) or mild residual disease (H-2b, H-2d, H-2q). Inter-line differences within the latter group varied between experiments such that no clear rank order emerged. Inexorable disease progression occurred in congenic BALB/B, BALB/c and BALB/K alike, although it was significantly slower in the latter line when infected with smaller doses. Genetic control of BALB/c susceptibility is predominantly in the non-H-2 background with only a minor H-2 linked regulatory influence on the later stage. C57BL/6, BALB/c and their F1 hybrid characteristically display healing, fatal progressive and non-healing lesions, respectively, over a wide dose range. BALB/c-like susceptibility segregates strictly in the F2 and backcross progeny according to a 1 predominant gene prediction. A comparison of the present data with those concerning genetic regulation of acute and chronic stages of systemic L. donovani infection in mice reveals differing control for the outcome of cutaneous L. tropica infection, in which other important genetic influences must be involved.