immunology of infectious and parasitic diseases - XXXVII Congress ...

HYPERNOCICEPTION DEVELOPMENT AND IMMUNE CELL INFILTRATION
IN DORSAL ROOT GANGLION OF MICE INFECTED WITH HSV-1
JAQUELINE RAYMONDI SILVA (1) ; ALEXANDRE HASHIMOTO PEREIRA
LOPES (1) ; JHIMMY TALBOT (1) ; RAFAEL FREITAS DE OLIVEIRA FRANÇA (1) ;
BENEDITO ANTONIO LOPES DA FONSECA (1) ; THIAGO MATTAR CUNHA (1) ;
FERNANDO DE QUEIRÓZ CUNHA (1)
(1) . Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo
Introduction: Herpes Zoster (HZ) is a disease caused by reactivation of latent
herpesvirus Varicella Zoster (VZV) in the sensory ganglion, characterized by
dermal rash and severe pain. VZV infects only humans, and there are no animal
models available to study the disease. However, when mice are inoculated with
herpes simplex virus type-1 (HSV-1) on the skin of the hind paw, they develop
HZ-like skin lesions and show pain-related responses to noxious mechanical
stimulation and innocuous tactile stimulus. For this reason, this model has been
used to study the pathophysiology of herpes zoster. So far, there are no data
available about the immune response in dorsal root ganglion (DRG) of mice
infected with HSV-1 in this model. Thus, the aim of this study was to evaluate
cells and inflammatory mediators present in DRGs and its relationship with
hypernociception during HSV-1 cutaneous infection.
Methods and results: Briefly, mice were depilated with a chemical depilatory
and three days later 2 x 10 5 plaque forming unities (PFU) of HSV-1 were
inoculated in the skin of the right hind paw after scarification. Mice were
observed daily and behavioral tests were performed from 0-21 day post
inoculation. The DRGs L1-L6 were collected at 7, 15 and 21days post infection
(dpi) and flow citometry analysis and RT-PCR were performed. Viral load was
measured by quantitative Real-Time PCR. Mice developed hypernociception
from 3 to 21 dpi in the ipsilateral (ips) paws, but not in the contralateral (cl)
paws. A higher viral load was detected in DRGs L3, L4 and L5 of infected mice
at 7 dpi, when compared to control or naïve mice. We observed an
inflammatory infiltrate composed by CD4+, CD8+, CD11b+, Gr1+ cells in DRGs
L4, L5 and L6, but not in spinal cord. In infected mice, a higher expression of
COX-2 and TNF- was detected in DRGs L4, L5 and L6 of ips paws at 7 dpi,
but not at 15 and 21 dpi. However, GFAP expression was not detected at 7 dpi,
but was increased at 15 and 21 dpi, when compared to naïve mice.
Conclusions: Our results show the presence of an intense inflammatory
infiltrate, composed by cells from immune system, in DRGs of infected mice,
and the early expression of inflammatory mediators in this local that might
contribute for the induction of hypernociception in this model.
Financial support: FAPESP (2010/12309-8)