Genetic predisposition to self-curing infection with the protozoan Leishmania chagasi: a genomewide scan

Abstract

The protozoan Leishmania chagasi can cause disseminated, fatal visceral leishmaniasis (VL) or asymptomatic infection in humans. We hypothesized that host genetic factors contribute to this variable response to infection. A family study was performed in neighborhoods of endemicity for L. chagasi near Natal in northeastern Brazil. Study subjects were assessed for the presence of VL or asymptomatic infection, which was defined by a positive delayed-type hypersensitivity (DTH) skin test response to Leishmania antigen without disease symptoms. A genomewide panel of 385 autosomal microsatellite markers in 1254 subjects from 191 families was analyzed to identify regions of linkage. Regions with potential linkage to the DTH response on chromosomes 15 and 19, as well as a novel region on chromosome 9 with potential linkage to VL, were identified. Understanding the genetic factors that determine whether an individual will develop symptomatic or asymptomatic infection with L. chagasi may identify proteins essential for immune protection against this parasitic disease and reveal strategies for immunotherapy or prevention.

Figure 1

Summary of genome scan results for symptomatic visceral leishmaniasis and the size of Montenegro response. The X axis represents the distance in centiMorgans (cM) for each chromosome using the Marshfield genetic maps. Multipoint graphs of the LOD score for VL and the DTH (Montenegro) immune response. The solid line depicts the non-parametric linkage analysis of the VL phenotype. The dashed line shows results of variance components analysis of the size of Montenegro (DTH) skin test response, corrected for age and gender.