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Bilateral approach to estimate the parasite and domestic dog genetic background in the expression of the response to the Leishmania infantum infection: from the genetic basis to the epidemiological impact

Grant number: 22/16578-0
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): June 01, 2023
Effective date (End): May 31, 2024
Field of knowledge:Biological Sciences - Genetics - Animal Genetics
Principal Investigator:Marcia Dalastra Laurenti
Grantee:Luís Fábio da Silva Batista
Supervisor: Daniel Jeffares
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of York, England  
Associated to the scholarship:20/10430-6 - Genomic approaches to explore the consequences of the interaction of biologically distinct Leishmania infantum genotypes with vertebrate hosts and the impact on the epidemiology of the American Visceral Leishmaniasis, BP.PD

Abstract

Genetic diversity of the host-parasite interplay may be associated with differences in disease outcome, resistance to treatment and eco-epidemiological traits. Deletion of a >12kb loci on chromosome 31 of L. infantum has been associated with resistance to treatment in visceral leishmaniasis (VL). Named Mitelfosine Sensitive Loci (MSL), this chromosomal segment includes genes related to virulence. Our group has been studying the immunogenetics and molecular epidemiology of the canine visceral leishmaniasis (CVL) and has observed that the MSL deletion-carrying isolates (DEL) were abundantly distributed in at least 15 Brazilian states, while the Non-DEL was present only in 6 states. Such dispersion may be related to the hypothesis that DEL would cause a mild infection, with a lower parasitic load, less detectable in diagnostic tests. Dogs infected with DEL would remain for long-term in endemic area, contributing to the maintenance of the VL transmission. In fact, preliminary data indicated that dogs infected with DEL had significantly lower parasite load, IgG and IgA levels than dogs infected with Non-DEL. Furthermore, DEL infection was significantly more common among dogs carrying the SNP allele previously associated with low IgG levels, a typical trait of dogs with subclinical infection, corroborating with the hypothesis. The research group of the supervisor of this internship proposal employed methods of heritability, genetic structure, genome-wide association study (GWAS) and observed that genetic variants of L. infantum are the main predictors of mortality caused by VL. However, the participation of the parasite-host genetic basis has not been explored in an integrated way. A bilateral approach able to estimating the proportion of the clinical-immunological response of dogs to L. Infantum infection explained by the parasite and host genetics and their epidemiological impact can generate useful data for the improvement of vaccine, diagnosis and control of the VL actions. (AU)

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