Leishmania amazonensis downregulates macrophage iNOS expression via Histone Deacetylase 1 (HDAC1): a novel parasite evasion mechanism

Autor(es):Mostrar menos -

Calegari-Silva, Teresa C. ^[1] ; Vivarini, Aislan C. ^[1] ; Pereira, Renata de M. S. ^[1] ; Dias-Teixeira, Karina L. ^[1] ; Rath, Carolina T. ^[1] ; Pacheco, Amanda S. S. ^[1] ; Silva, Gabrielle B. L. ^[1] ; Pinto, Charlene A. S. ^[1] ; dos Santos, Jose V. ^[1] ; Saliba, Alessandra M. ^[2] ; Corbett, Carlos E. P. ^[3] ; de Castro Gomes, Claudia M. ^[3] ; Fasel, Nicolas ^[4] ; Lopes, Ulisses G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Mol Parasitol Lab, CCS, Cidade Univ, BR-21949900 Rio de Janeiro, RJ - Brazil

^[2] Univ Estado Rio de Janeiro, Fac Ciencias Med, Dept Microbiol & Parasitol, Rio De Janeiro - Brazil

^[3] Univ Sao Paulo, Fac Med, Dept Patol, Sao Paulo - Brazil

^[4] Univ Lausanne, Dept Biochem, Epalinges - Switzerland

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Immunology; v. 48, n. 7, p. 1188-1198, JUL 2018.
• Citações Web of Science: 3

Resumo

The induced expression of nitric oxide synthase (iNOS) controls the intracellular growth of Leishmania in infected macrophages. Histones deacetylases (HDACs) negatively regulate gene expression through the formation of complexes containing transcription factors such as NF-B p50/50. Herein, we demonstrated the occupancy of p50/p50\_HDAC1 to iNOS promoter associated with reduced levels of H3K9Ac. Remarkably, we found increased levels of HDAC1 in L. amazonensis-infected macrophages. HDAC1 upregulation was not found in L. major-infected macrophages. The parasite intracellular load was reduced in HDAC1 knocked-down macrophages, which presented increased nitric oxide levels. HDAC1 silencing led to the occupancy of CBP/p300 to iNOS promoter and the rise of H3K9Ac modification. Importantly, the immunostaining of skin samples from hiporeactive cutaneous leishmaniasis patients infected with L. amazonensis, revealed high levels of HDAC1. In brief, L. amazonensis induces HDAC1 in infected macrophages, which contribute to parasite survival and is associated to hiporeactive stage found in L. amazonensis infected patients. (AU)

• Processo FAPESP: 14/50315-0 - Leishmanioses na América Latina: uma perspectiva avançada sobre fatores imunopatogenéticos da infecção cutânea e visceral, imunomoduladores da saliva de vetores flebotomíneos e exo-antígenos imunogênicos de Leishmania (L.) infantum chagasi candidatos à vacina
• Beneficiário: Marcia Dalastra Laurenti
• Modalidade de apoio: Auxílio à Pesquisa - Temático