Variants of CARD8 in Leishmania guyanensis-cutaneous leishmaniasis and influence of the variants genotypes on circulating plasma cytokines IL-1β, TNFα and IL-8.

Autor: Sequera HDG; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil., Souza JL; Faculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, Brazil.; Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, Brazil., Junior JDES; Faculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, Brazil.; Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, Brazil., Silva LSD; 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., Pinheiro SK; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil.; Faculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, Brazil., Kerr HKA; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil., Souza MLG; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, 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., 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., Ramasawmy R; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, 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.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil.; Genomic Health Surveillance Network: Optimization of Assistance and Research in the State of Amazonas (REGESAM), Manaus, Brazil.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2023 Jun 05; Vol. 17 (6), pp. e0011416. Date of Electronic Publication: 2023 Jun 05 (Print Publication: 2023).
DOI: 10.1371/journal.pntd.0011416
Abstrakt: Nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein family (NLR) are intracellular pathogen recognition receptors mediating innate immunity, releasing proinflammatory cytokines IL-1β and IL-18, and promoting pyroptotic cell death, upon sensing pathogenic or endogenous danger signals. In animal models, NLRP3 inflammasome has a dual role, pathogenic or protective in Leishmania-infection, depending on the Leishmania species and mice strain. Caspase recruitment containing domain 8 (CARD8) is a negative regulator of NLRP3 inflammasome and also an inhibitor of transcription factor NFĸB, a major transcription factor of proinflammatory cytokines. We investigated whether single nucleotide variants in CARD8 may partially explain why only a proportion of individuals coming from the same area of endemicity of leishmaniasis develop cutaneous leishmaniasis caused by Leishmania guyanensis. We genotyped four single nucleotide variants of the CARD8 gene by direct nucleotide sequencing in 1741 individuals from an endemic area of leishmaniasis, constituting 850 patients with CL and 891 healthy controls. The frequencies of the genotypes of the variants rs2288877 T>C, rs73944113 C>T, and rs2043211 A>T are similar among the patients with CL and HC, while the variant rs2288876 A>G) reveals an excess of the genotype AA among the patients with CL (44%) compared to 37% in the HC group. Allele A of the variant rs2288876 A>G) is associated with susceptibility to CL (OR = 1.2 [95%CI 1.03-1.4]; P = 0.01). Haplotype analysis showed that individuals harboring the haplotype CCAA have 280% odds of developing CL caused by L. guyanensis (OR = 3.8 [95% CI 2.0-7.7]; p = 0.00004). The variants rs2288877 T>C and rs2288876 A>G correlate with the plasma level of IL-8. Spearman correlation showed a significant positive correlation between the rs2288876 A>G allele A and the level of IL-8 (ρ = 0.22; p = 0.0002). CARD8 may partially contribute to the development of CL caused by L. guyanensis.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Sequera 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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