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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Tolerogenic Plasmacytoid Dendritic Cells Control Paracoccidioides brasiliensis Infection by Inducting Regulatory T Cells in an IDO-Dependent Manner

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Autor(es):
de Araujo, Eliseu Frank ; Medeiros, Daniella Helena ; de Lima Galdino, Nayane Alves ; Condino-Neto, Antonio ; Garcia Calich, Vera Lucia ; Loures, Flavio Vieira
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: PLOS PATHOGENS; v. 12, n. 12 DEC 2016.
Citações Web of Science: 11
Resumo

Plasmacytoid dendritic cells (pDCs), considered critical for immunity against viruses, were recently associated with defense mechanisms against fungal infections. However, the immunomodulatory function of pDCs in pulmonary paracoccidiodomycosis (PCM), an endemic fungal infection of Latin America, has been poorly defined. Here, we investigated the role of pDCs in the pathogenesis of PCM caused by the infection of 129Sv mice with 1 x 10(6) P. brasiliensis-yeasts. In vitro experiments showed that P. brasiliensis infection induces the maturation of pDCs and elevated synthesis of TNF-alpha and IFN-beta. The in vivo infection caused a significant influx of pDCs to the lungs and increased levels of pulmonary type I IFN. Depletion of pDCs by a specific monoclonal antibody resulted in a less severe infection, reduced tissue pathology and increased survival time of infected mice. An increased influx of macrophages and neutrophils and elevated presence of CD4(+) and CD8(+) T lymphocytes expressing IFN-gamma and IL-17 in the lungs of pDC-depleted mice were also observed. These findings were concomitant with decreased frequency of Treg cells and reduced levels of immunoregulatory cytokines such as IL-10, TGF-beta, IL-27 and IL-35. Importantly, P. brasilienis infection increased the numbers of pulmonary pDCs expressing indoleamine 2,3-dioxygenase-1 (IDO), an enzyme with immunoregulatory properties, that were reduced following pDC depletion. In agreement, an increased immunogenic activity of infected pDCs was observed when IDO-deficient or IDO-inhibited pDCs were employed in co-cultures with lymphocytes Altogether, our results suggest that in pulmonary PCM pDCs exert a tolerogenic function by an IDO-mediated mechanism that increases Treg activity. (AU)

Processo FAPESP: 14/18668-0 - A importância do receptor para aril hidrocarboneto (AhR) na regulação da resposta imune e na resistência de hospedeiros à paracoccidioidomicose pulmonar
Beneficiário:Eliseu Frank de Araujo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 14/22630-9 - Estudo da função das células dendríticas plasmocitóides e mielóides frente à infecção pelo fungo Paracoccidioides Brasiliensis
Beneficiário:Flávio Vieira Loures
Linha de fomento: Bolsas no Brasil - Apoio a Jovens Pesquisadores
Processo FAPESP: 15/12328-6 - Função dos interferons do tipo I na PCM pulmonar murina: avaliação comparativa da gravidade da doença entre camundongos controle e nocautes para IFN-aBR
Beneficiário:Daniella Helena Medeiros
Linha de fomento: Bolsas no Brasil - Iniciação Científica