Influence of H–2 complex on acquired resistance to Leishmania donovani infection in mice

Abstract

Innate susceptibility to Leishmania donovani infection in mice (measured over 2--4 weeks) is under the control of a single autosomal gene (Lsh) segregating for incompletely dominant resistant (r) and recessive susceptible (s) alleles. This locus maps away from the known histocompatibility loci to a position between the centromere and Id-1 on the chromosome 1 of the mouse. Amongst homozygous recessive Lsh strains of mice two patterns of recovery are observed when the course of infection is followed over a longer term. In some strains a dramatic fall in parasite numbers with histological liver damage occurs while other strains maintain immense parasite loads for up to two years involving mononuclear phagocytes throughout the body. We now present evidence which suggests that this difference in long-term response is largely controlled by a gene(s) within, or closely adjacent to, the major histocompatibility complex (H-2) of the mouse.

The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene.

“…Although genetic factors have been implicated in resistance to benign and acute forms of leishmaniasis (7,38,39), the clearest manifestation of genetic control is for visceral leishmaniasis caused by L. donovani. While some mouse strains allow rapid proliferation of the parasites in liver, others completely inhibit parasite growth.…”

Genetic analysis of multicase families of visceral leishmaniasis in northeastern Brazil: no major role for class II or class III regions of HLA

“…This is of interest considering the previous genetic and functional studies in mice. 6,8,9 Also in view of the major role which class I and II genes of the MHC have in presenting antigen to protective or disease exacerbatory CD4 30,31 or CD8 32 T cells, and the high levels of circulating TNF␣ associated with clinical disease in man. 10 There are, of course, many other genes/ mechanisms that regulate these important immunological pathways.…”

“…6 Genetic mapping data 6,7 are supported by functional data showing that treatment in vivo with anti-IE monoclonal antibodies abrogates the non-cure response of IE-bearing H-2 d mice. 8 Treatment of H-2 b mice, which do not express IE, with monoclonal antibodies to IA reduces their ability to clear liver and spleen parasite burdens and self-cure.…”

Major histocompatibility complex and its importance towards controlling infection

“…176 Due to advances in science and technology, there is evidence to support the fact that the genetic background of the host and the immune response play an important role in the outcome of the leishmaniasis disease. [176][177][178][179][180][181][182][183][184][185][186] One of the first studies assessing the potential association between HLA and cutaneous leishmaniasis involving serological methods was under taken in France, with Leishmania guyanensis. 180 The study revealed the association of a low HLA-Cw7 frequency with pathogenesis of cutaneous leishmaniasis.…”