{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T20:10:22Z","timestamp":1767989422383,"version":"3.49.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo e Pesquisa do Estado do Amazonas","award":["FAPEAM RESOLU\u00c7\u00c3O N. 002\/2008, 007|2018 e 005|2019 \u2013 PR\u00d3-ESTADO"],"award-info":[{"award-number":["FAPEAM RESOLU\u00c7\u00c3O N. 002\/2008, 007|2018 e 005|2019 \u2013 PR\u00d3-ESTADO"]}]},{"name":"Funda\u00e7\u00e3o de Amparo e Pesquisa do Estado do Amazonas","award":["06200151\/2020"],"award-info":[{"award-number":["06200151\/2020"]}]},{"name":"Funda\u00e7\u00e3o de Amparo e Pesquisa do Estado do Amazonas","award":["01.02.016301.03393\/2021-80"],"award-info":[{"award-number":["01.02.016301.03393\/2021-80"]}]},{"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"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Leishmaniases, a group of vector-borne diseases, are caused by the protozoan intracellular parasite <jats:italic>Leishmania<\/jats:italic> (<jats:italic>L<\/jats:italic>.) and are transmitted by the phlebotomine sandflies. A wide range of clinical manifestations in <jats:italic>L<\/jats:italic>- infection is observed. The clinical outcome ranges from asymptomatic, cutaneous leishmaniasis (CL) to severe mucosal leishmaniasis (ML) or visceral leishmaniasis (VL), depending on the <jats:italic>L<\/jats:italic>. species. Interestingly, only a fraction of <jats:italic>L<\/jats:italic>.-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 <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic>. We investigated whether variants in the <jats:italic>NOD2<\/jats:italic> gene (R702W rs2066844, G908R rs2066845, and L1007fsinsC rs2066847) are associated with susceptibility to CL caused by <jats:italic>L<\/jats:italic>. <jats:italic>guyanensis (Lg)<\/jats:italic> in 837 patients with <jats:italic>Lg<\/jats:italic>-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 <jats:italic>Lg<\/jats:italic>-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 <jats:italic>Lg<\/jats:italic>-CL and HC, respectively. None of the variants revealed any association with susceptibility to the development of <jats:italic>Lg<\/jats:italic>-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-\u03b3. G908R heterozygotes also tend to have low IFN-\u03b3, TNF-\u03b1, IL-17, and IL-8. Variants of <jats:italic>NOD2<\/jats:italic> are not involved in the pathogenesis of <jats:italic>Lg-<\/jats:italic>CL.<\/jats:p>","DOI":"10.1371\/journal.pone.0281814","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T18:35:20Z","timestamp":1676572520000},"page":"e0281814","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Variants of NOD2 in Leishmania guyanensis-infected patients with cutaneous leishmaniasis and correlations with plasma circulating pro-inflammatory cytokines"],"prefix":"10.1371","volume":"18","author":[{"given":"Tirza Gabrielle Ramos de","family":"Mesquita","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 do Esp\u00edrito Santo","family":"Junior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josu\u00e9 Lacerda de","family":"Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lener Santos da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuanny Arruda do","family":"Nascimento","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"}]},{"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":[[2023,2,16]]},"reference":[{"key":"pone.0281814.ref001","unstructured":"World Health Organization. https:\/\/www.who.int\/publications\/i\/item\/who-wer9525 (accessed on 20 June 2022)."},{"key":"pone.0281814.ref002","unstructured":"Minist\u00e9rio da Sa\u00fade do Brasil. 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