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

Márcia Carvalho Vilela, Graciela Kunrath Lima, David Henrique Rodrigues, Norinne Lacerda-Queiroz, Vinicius Sousa Pietra Pedroso, Aline Silva de Miranda, Milene Alvarenga Rachid, Erna Geessien Kroon, Marco Antônio Campos, Mauro Martins Teixeira, Antonio Lucio Teixeira

Producción científica: Articlerevisión exhaustiva

7 Citas (Scopus)


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 104 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.

Idioma originalEnglish (US)
Páginas (desde-hasta)613-621
Número de páginas9
PublicaciónJournal of Neuroimmune Pharmacology
EstadoPublished - dic 1 2016
Publicado de forma externa

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology


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