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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 14
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: European Journal of Immunology; v. 48, n. 7, p. 1188-1198, JUL 2018.
Web of Science Citations: 3
Abstract

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)

FAPESP's process: 14/50315-0 - Leishmaniasis in Latin America: an advanced perspective on immunopathogenetic factors of cutaneous and visceral infection, immunomodulators of the sandflies vector saliva and immunogenic exo-antigens of Leishmania (L.) infantum chagasi as vaccine candidates
Grantee:Marcia Dalastra Laurenti
Support Opportunities: Research Projects - Thematic Grants