Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection
Open Access
- 25 August 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Immunogenetics
- Vol. 61 (9), 619-633
- https://doi.org/10.1007/s00251-009-0392-9
Abstract
Elimination of pathogens is the basis of host resistance to infections; however, relationship between persisting pathogens and disease has not been clarified. Leishmania major infection in mice is an important model of host–pathogen relationship. Infected BALB/c mice exhibit high parasite numbers in lymph nodes and spleens, and a chronic disease with skin lesions, splenomegaly, and hepatomegaly, increased serum IgE levels and cytokine imbalance. Although numerous gene loci affecting these disease symptoms have been reported, genes controlling parasites’ elimination or dissemination have never been mapped. We therefore compared genetics of the clinical and immunologic symptomatology with parasite load in (BALB/c × CcS-11) F2 hybrids and mapped five loci, two of which control parasite elimination or dissemination. Lmr5 influences parasite loads in spleens (and skin lesions, splenomegaly, and serum IgE, IL-4, and IFNγ levels), and Lmr20 determines parasite numbers in draining lymph nodes (and serum levels of IgE and IFNγ), but no skin or visceral pathology. Three additional loci do not affect parasite numbers but influence significantly the disease phenotype—Lmr21: skin lesions and IFNγ levels, Lmr22: IL-4 levels, Lmr23: IFNγ levels, indicating that development of L. major-caused disease includes critical regulations additional to control of parasite spread.Keywords
This publication has 58 references indexed in Scilit:
- Genetic susceptibility to infectious disease: lessons from mouse models of leishmaniasisNature Reviews Genetics, 2006
- Genetics of susceptibility to leishmaniasis in mice: four novel loci and functional heterogeneity of gene effectsGenes & Immunity, 2006
- Linkage analysis of the genetic determinants of T-cell IL-4 secretion, and identification of Flj20274 as a putative candidate geneGenes & Immunity, 2005
- Mapping Quantitative Trait Loci for Anxiety in Chromosome Substitution Strains of MiceGenetics, 2005
- A Locus on Mouse Chromosome 6 That Determines Resistance to Herpes Simplex Virus Also Influences Reactivation, While an Unlinked Locus Augments Resistance of Female MiceJournal of Virology, 2003
- Different Genetic Control of Cutaneous and Visceral Disease after Leishmania major Infection in MiceInfection and Immunity, 2003
- Genetic polymorphisms in mouse genes regulating age-sensitive and age-stable T cell subsetsGenes & Immunity, 2003
- Separation and mapping of multiple genes that control IgE level in Leishmania major infected miceGenes & Immunity, 2002
- IL-2-Induced Proliferative Response Is Controlled by LociCinda1andCinda2on Mouse Chromosomes 11 and 12: A Distinct Control of the Response Induced by Different IL-2 ConcentrationsGenomics, 1997
- Genetic Dissection of Complex TraitsScience, 1994