{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:08:15Z","timestamp":1767179295300,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011416","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["404181\/2012-0"],"award-info":[{"award-number":["404181\/2012-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004916","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas","doi-asserted-by":"publisher","award":["06200151\/2020"],"award-info":[{"award-number":["06200151\/2020"]}],"id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004916","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas","doi-asserted-by":"publisher","award":["01.02.016301.03393\/2021-80"],"award-info":[{"award-number":["01.02.016301.03393\/2021-80"]}],"id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004916","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas","doi-asserted-by":"publisher","award":["FAPEAM RESOLU\u00c7\u00c3O N. 002\/2008, 007\/2018, e 005\/2019 - PRO-ESTSDO"],"award-info":[{"award-number":["FAPEAM RESOLU\u00c7\u00c3O N. 002\/2008, 007\/2018, e 005\/2019 - PRO-ESTSDO"]}],"id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein family (NLR) are intracellular pathogen recognition receptors mediating innate immunity, releasing proinflammatory cytokines IL-1\u03b2 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\n                    <jats:italic>Leishmania<\/jats:italic>\n                    -infection, depending on the\n                    <jats:italic>Leishmania<\/jats:italic>\n                    species and mice strain. Caspase recruitment containing domain 8 (CARD8) is a negative regulator of NLRP3 inflammasome and also an inhibitor of transcription factor NF\u0138B, a major transcription factor of proinflammatory cytokines. We investigated whether single nucleotide variants in\n                    <jats:italic>CARD8<\/jats:italic>\n                    may partially explain why only a proportion of individuals coming from the same area of endemicity of leishmaniasis develop cutaneous leishmaniasis caused by\n                    <jats:italic>Leishmania guyanensis<\/jats:italic>\n                    . We genotyped four single nucleotide variants of the\n                    <jats:italic>CARD8<\/jats:italic>\n                    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&gt;C, rs73944113 C&gt;T, and rs2043211 A&gt;T are similar among the patients with CL and HC, while the variant rs2288876 A&gt;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&gt;G) is associated with susceptibility to CL (OR = 1.2 [95%CI 1.03\u20131.4]; P = 0.01). Haplotype analysis showed that individuals harboring the haplotype CCAA have 280% odds of developing CL caused by\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>guyanensis<\/jats:italic>\n                    (OR = 3.8 [95% CI 2.0\u20137.7]; p = 0.00004). The variants rs2288877 T&gt;C and rs2288876 A&gt;G correlate with the plasma level of IL-8. Spearman correlation showed a significant positive correlation between the rs2288876 A&gt;G allele A and the level of IL-8 (\u03c1 = 0.22; p = 0.0002).\n                    <jats:italic>CARD8<\/jats:italic>\n                    may partially contribute to the development of CL caused by\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>guyanensis<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0011416","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T13:28:00Z","timestamp":1685971680000},"page":"e0011416","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Variants of CARD8 in Leishmania guyanensis-cutaneous leishmaniasis and influence of the variants genotypes on circulating plasma cytokines IL-1\u03b2, TNF\u03b1 and IL-8"],"prefix":"10.1371","volume":"17","author":[{"given":"H\u00e9ctor David Graterol","family":"Sequera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josu\u00e9 Lacerda de","family":"Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 do Esp\u00edrito Santo","family":"Junior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lener Santos da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzana Kanawati","family":"Pinheiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herllon Karllos Athaydes","family":"Kerr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara L\u00facia Gomes de","family":"Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus Vinitius de Farias","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tirza Gabrielle Ramos de","family":"Mesquita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0538-0773","authenticated-orcid":true,"given":"Rajendranath","family":"Ramasawmy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,6,5]]},"reference":[{"key":"pntd.0011416.ref001","doi-asserted-by":"crossref","first-page":"750","DOI":"10.12688\/f1000research.11120.1","article-title":"Leishmaniasis: a review.","volume":"6","author":"E Torres-Guerrero","year":"2017","journal-title":"F1000Research."},{"key":"pntd.0011416.ref002","volume-title":"Leishmaniasis [Internet]. 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