Genetic predisposition to self-curing infection with the protozoan Leishmania chagasi: a genomewide scan.
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.
Jeronimo
Selma M B
SM
Department of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, Rio de Grande do Norte, Brazil.
Duggal
Priya
P
Ettinger
Nicholas A
NA
Nascimento
Eliana T
ET
Monteiro
Gloria R
GR
Cabral
Angela P
AP
Pontes
Nubia N
NN
Lacerda
Henio G
HG
Queiroz
Paula V
PV
Gomes
Carlos E M
CE
Pearson
Richard D
RD
Blackwell
Jenefer M
JM
Beaty
Terri H
TH
Wilson
Mary E
ME
D000293:Adolescent; D000818:Animals; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D019353:Endemic Diseases; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics*; D007223:Infant; D007891:Leishmania / Q000472:pathogenicity*; D007896:Leishmaniasis / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D010641:Phenotype