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The TIGIT+ T regulatory cells subset associates with nosocomial infection and fatal outcome in COVID-19 patients under mechanical ventilation

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de Lima, Mikhael Haruo Fernandes ; Machado, Caio Cavalcante ; Nascimento, Daniele Carvalho ; Silva, Camila Meirelles S. ; Toller-Kawahisa, Juliana Escher ; Rodrigues, Tamara Silva ; Veras, Flavio Protassio ; Pontelli, Marjorie Cornejo ; Castro, Italo A. ; Zamboni, Dario Simoes ; Filho, Jose-Carlos A. ; Cunha, Thiago M. ; Arruda, Eurico ; da Cunha, Larissa Dias ; Oliveira, Rene D. R. ; Cunha, Fernando Q. ; Louzada-Junior, Paulo
Número total de Autores: 17
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 13, n. 1, p. 12-pg., 2023-08-21.
Resumo

The TIGIT(+)FOXP3(+)Treg subset (TIGIT(+)Tregs) exerts robust suppressive activity on cellular immunity and predisposes septic individuals to opportunistic infection. We hypothesized that TIGIT(+)Tregs could play an important role in intensifying the COVID-19 severity and hampering the defense against nosocomial infections during hospitalization. Herein we aimed to verify the association between the levels of the TIGIT(+)Tregs with the mechanical ventilation requirement, fatal outcome, and bacteremia during hospitalization. TIGIT(+)Tregs were immunophenotyped by flow cytometry from the peripheral blood of 72 unvaccinated hospitalized COVID-19 patients at admission from May 29th to August 6th, 2020. The patients were stratified during hospitalization according to their mechanical ventilation requirement and fatal outcome. COVID-19 resulted in a high prevalence of the TIGIT(+)Tregs at admission, which progressively increased in patients with mechanical ventilation needs and fatal outcomes. The prevalence of TIGIT(+)Tregs positively correlated with poor pulmonary function and higher plasma levels of LDH, HMGB1, FGL2, and TNF. The non-survivors presented higher plasma levels of IL-33, HMGB1, FGL2, IL-10, IL-6, and 5.54 times more bacteremia than survivors. Conclusions: The expansion of the TIGIT(+)Tregs in COVID-19 patients was associated with inflammation, lung dysfunction, bacteremia, and fatal outcome. (AU)

Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 20/02642-3 - Caracterização da subpopulação de células T reguladoras TIGIT+ na resposta à terapia com drogas anti-reumátidas modificadoras de doença em pacientes com Artrite Reumatoide
Beneficiário:Mikhael Haruo Fernandes de Lima
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado