Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis.

Autor: Vilela MC; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil. marciacvilela@gmail.com.; Departamento de Ciências Básicas da Vida, Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brazil. marciacvilela@gmail.com., Lima GK; Departamento de Microbiologia, ICB/UFMG, Belo Horizonte, Brazil., Rodrigues DH; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil.; Departamento de Ciências Básicas da Vida, Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brazil., Lacerda-Queiroz N; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil., Pedroso VS; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil., de Miranda AS; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil.; Departamento de Morfologia, ICB/UFMG, Belo Horizonte, Brazil., Rachid MA; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil.; Departamento de Patologia Geral, ICB/UFMG, Belo Horizonte, Brazil., Kroon EG; Departamento de Microbiologia, ICB/UFMG, Belo Horizonte, Brazil., Campos MA; Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Brazil., Teixeira MM; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil., Teixeira AL; Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 30130-100 Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, Brazil. altexjr@hotmail.com.
Jazyk: angličtina
Zdroj: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology [J Neuroimmune Pharmacol] 2016 Dec; Vol. 11 (4), pp. 613-621. Date of Electronic Publication: 2016 May 19.
DOI: 10.1007/s11481-016-9684-7
Abstrakt: Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The exacerbated immune response against the virus contributes to the disease severity and death. Platelet activating factor (PAF) is a mediator capable of inducing increase in vascular permeability, production of cytokines on endothelial cells and leukocytes. We aimed to investigate the activation of PAF receptor (PAFR) and its contribution to the severity of the inflammatory response in the brain following HSV-1 infection. C57BL/6 wild-type (WT) and PAFR deficient (PAFR -/- ) mice were inoculated intracranially with 10 4 plaque-forming units (PFU) of HSV-1. Visualization of leukocyte recruitment was performed using intravital microscopy. Cells infiltration in the brain tissue were analyzed by flow cytometry. Brain was removed for chemokine assessment by ELISA and for histopathological analysis. The pharmacological inhibition by the PAFR antagonist UK-74,505 was also analyzed. In PAFR -/- mice, there was delayed lethality but no difference in viral load. Histopathological analysis of infected PAFR -/- mice showed that brain lesions were less severe when compared to their WT counterparts. Moreover, PAFR -/- mice showed less TCD4 + , TCD8 + and macrophages in brain tissue. This reduction of the presence of leukocytes in parenchyma may be mechanistically explained by a decrease in leukocytes rolling and adhesion. PAFR -/- mice also presented a reduction of the chemokine CXCL9 in the brain. In addition, by antagonizing PAFR, survival of C57BL/6 infected mice increased. Altogether, our data suggest that PAFR plays a role in the pathogenesis of experimental HSV-1 meningoencephalitis, and its blockade prevents severe disease manifestation.
Databáze: MEDLINE
Externí odkaz: