Variants of NOD2 in Leishmania guyanensis-infected patients with cutaneous leishmaniasis and correlations with plasma circulating pro-inflammatory cytokines.

Autor: Mesquita TGR; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil., Junior JDES; Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.; Faculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, Brazil., Souza JL; Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.; Faculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, Brazil., Silva LSD; Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazonia Legal (Rede Bionorte), Universidade do Estado do Amazonas, Manaus, Brazil., Nascimento TAD; Faculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, Brazil., Souza MLG; Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil., Guerra MVF; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil., Ramasawmy R; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil.; Faculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, Brazil.; Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazonia Legal (Rede Bionorte), Universidade do Estado do Amazonas, Manaus, Brazil.; Genomic Health Surveillance Network: Optimization of Assistance and Research in The State of Amazonas - REGESAM, Manaus, Amazonas, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Feb 16; Vol. 18 (2), pp. e0281814. Date of Electronic Publication: 2023 Feb 16 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0281814
Abstrakt: Leishmaniases, a group of vector-borne diseases, are caused by the protozoan intracellular parasite Leishmania (L.) and are transmitted by the phlebotomine sandflies. A wide range of clinical manifestations in L- infection is observed. The clinical outcome ranges from asymptomatic, cutaneous leishmaniasis (CL) to severe mucosal leishmaniasis (ML) or visceral leishmaniasis (VL), depending on the L. species. Interestingly, only a fraction of L.-infected individuals progress to disease development, suggesting a key role of host genetics in the clinical outcome. NOD2 plays a critical role in the control of host defense and inflammation. The NOD2-RIK2 pathway is involved in developing a Th1- type response in patients with VL and C57BL/6 mice infected with L. infantum. We investigated whether variants in the NOD2 gene (R702W rs2066844, G908R rs2066845, and L1007fsinsC rs2066847) are associated with susceptibility to CL caused by L. guyanensis (Lg) in 837 patients with Lg-Cl and 797 healthy controls (HC) with no history of leishmaniasis. Both patients and HC are from the same endemic area of the Amazonas state of Brazil. The variants R702W and G908R were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and L1007fsinsC was by direct nucleotide sequencing. The minor allele frequency (MAF) of L1007fsinsC was 0.5% among the patients with Lg-CL and 0.6% in the healthy controls group. R702W genotypes frequencies were similar in both groups. Only 1% and 1.6% were heterozygous for G908R among the patients with Lg-CL and HC, respectively. None of the variants revealed any association with susceptibility to the development of Lg-CL. Correlations of genotypes with the level of plasma cytokines revealed that individuals with the mutant alleles of R702W tend to have low levels of IFN-γ. G908R heterozygotes also tend to have low IFN-γ, TNF-α, IL-17, and IL-8. Variants of NOD2 are not involved in the pathogenesis of Lg-CL.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Mesquita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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