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Mapping of regulatory polymorphisms in the interaction between Mycobacterium leprae and macrophages.

Abstract

Leprosy is a complex disease caused by Mycobacterium leprae with high prevalence in Brazil. The pathogen is intracellular and has a preference for macrophages and Schwann cells. The genetic susceptibility to disease has been well demonstrated and is the subject of significant studies in the area, however, the data are still controversial and few genes have confirmed association in several populations. The high-throughput studies in genetic epidemiology have provided important data but do not further clarify the genetic architecture of susceptibility to the disease. Thus, we propose a different approach to identify loci associated to the disease based on the eQTLs (expression quantitative trait loci) mapping controlling the response of the innate immune cells which are decisive in the host response against the pathogen. We hope that studying biological phenotypes in the host parasite interaction, which are more controlled and less dependent on other determinants of susceptibility, we can find candidate loci and pathways for association with the disease. These data should be validated by studies that address the disease installation and its evolution and thus help to elucidate the genetic control of leprosy phenotypes, including the presence and absence of other non-genetic risk factors, in order to apply in prophylactic strategies and prognosis. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LEAL-CALVO, THYAGO; MARTINS, BRUNA LETICIA; BERTOLUCI, DANIELE FERREIRA; ROSA, PATRICIA SAMMARCO; DE CAMARGO, RODRIGO MENDES; GERMANO, GIOVANNA VALE; BRITO DE SOUZA, VANIA NIETO; PEREIRA LATINI, ANA CARLA; MORAES, MILTON OZORIO. Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection. FRONTIERS IN IMMUNOLOGY, v. 12, APR 16 2021. Web of Science Citations: 0.

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