{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T22:47:02Z","timestamp":1771454822850,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pedro Fernando da Costa Vasconcelos","award":["457664\/2013-4"],"award-info":[{"award-number":["457664\/2013-4"]}]},{"name":"Pedro Fernando da Costa Vasconcelos","award":["303999\/2016-0"],"award-info":[{"award-number":["303999\/2016-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Yellow fever (YF) may cause lesions in different organs. There are no studies regarding the in situ immune response in the human lung and investigating immunopathological aspects in fatal cases can help to better understand the evolution of the infection. Lung tissue samples were collected from 10 fatal cases of human yellow fever and three flavivirus-negative controls who died of other causes and whose lung parenchymal architecture was preserved. In YFV-positive fatal cases, the main histopathological changes included the massive presence of diffuse alveolar inflammatory infiltrate, in addition to congestion and severe hemorrhage. The immunohistochemical analysis of tissues in the lung parenchyma showed significantly higher expression of E-selectin, P-selectin, ICAM-1, VCAM-1 in addition to cytokines such as IL-4, IL-10, IL-13, TNF- \u03b1, IFN-\u03b3 and TGF-\u03b2 compared to the negative control. The increase in immunoglobulins ICAM-1 and VCAM-1 results in strengthening of tissue transmigration signaling. E-selectin and P-selectin actively participate in this process of cell migration and formation of the inflammatory infiltrate. IFN-\u03b3 and TNF-\u03b1 participate in the process of cell injury and viral clearance. The cytokines IL-4 and TGF-\u03b2, acting in synergism, participate in the process of tissue regeneration and breakdown. The anti-inflammatory cytokines IL-4, IL-10 and IL-13 also act in the reduction of inflammation and tissue repair. Our study indicates that the activation of the endothelium aggravates the inflammatory response by inducing the expression of adhesion molecules and cytokines that contribute to the rolling, recruitment, migration and eliciting of the inflammatory process in the lung parenchyma, contributing to the fatal outcome of the disease.<\/jats:p>","DOI":"10.3390\/v14112379","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T22:36:17Z","timestamp":1666910177000},"page":"2379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["New Insights into the Mechanism of Immune-Mediated Tissue Injury in Yellow Fever: The Role of Immunopathological and Endothelial Alterations in the Human Lung Parenchyma"],"prefix":"10.3390","volume":"14","author":[{"given":"Danielle Barbosa","family":"Vasconcelos","sequence":"first","affiliation":[{"name":"Sec\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas (IEC), Ananindeua 67015-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Fabio Magno","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Universidade do Estado do Par\u00e1 (UEPA), Bel\u00e9m 66050-540, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas Coutinho Tuma","family":"da Ponte","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Universidade do Estado do Par\u00e1 (UEPA), Bel\u00e9m 66050-540, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilla Costa","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Universidade do Estado do Par\u00e1 (UEPA), Bel\u00e9m 66050-540, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9400-2036","authenticated-orcid":false,"given":"Livia Caricio","family":"Martins","sequence":"additional","affiliation":[{"name":"Sec\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas (IEC), Ananindeua 67015-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0793-9665","authenticated-orcid":false,"given":"Bruno Tardelli Diniz","family":"Nunes","sequence":"additional","affiliation":[{"name":"Sec\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas (IEC), Ananindeua 67015-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9153-1234","authenticated-orcid":false,"given":"Arnaldo Jorge","family":"Martins Filho","sequence":"additional","affiliation":[{"name":"Sec\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas (IEC), Ananindeua 67015-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edna Cristina Santos","family":"Franco","sequence":"additional","affiliation":[{"name":"Sec\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas (IEC), Ananindeua 67015-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-6701","authenticated-orcid":false,"given":"Maria Irma Seixas","family":"Duarte","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade de S\u00e3o Paulo (USP), S\u00e3o Paulo 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Rodrigues de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Universidade do Estado do Par\u00e1 (UEPA), Bel\u00e9m 66050-540, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-5527","authenticated-orcid":false,"given":"Pedro Fernando da Costa","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Universidade do Estado do Par\u00e1 (UEPA), Bel\u00e9m 66050-540, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6267-9966","authenticated-orcid":false,"given":"Juarez Ant\u00f4nio Sim\u00f5es","family":"Quaresma","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Universidade do Estado do Par\u00e1 (UEPA), Bel\u00e9m 66050-540, Brazil"},{"name":"Faculdade de Medicina, Universidade de S\u00e3o Paulo (USP), S\u00e3o Paulo 66075-110, Brazil"},{"name":"N\u00facleo de Medicina Tropical, Universidade Federal do Par\u00e1 (UFPA), Bel\u00e9m 05508-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ol\u00edmpio, F.A., Falc\u00e3o, L.F.M., Carvalho, M.L.G., da 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