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

ROLE OF P2X7 RECEPTOR IN INNATE IMMUNE RESPONSE TO
Plasmodium chabaudi MALARIA
MARIA NOGUEIRA DE MENEZES; ÉRIKA MACHADO SALLES; ALEXANDRA
DOS ANJOS CASSADO; HENRIQUE BORGES SILVA; EDUARDO PINHEIRO
AMARAL; JOSÉ MARIA ÁLVAREZ; MARIA REGINA D‟IMPÉRIO LIMA
Immunology Department, Biomedical Science Institute, São Paulo University,
São Paulo.
Introduction: Malaria is characterized by intense activation of the immune
system that seems to contribute to protection against infection and to clinical
manifestations related to disease. ATP recognition by P2X7R in immune cells is
important for cell activation, death and migration. The main goal of this study is
to evaluate the effects of P2X7R-mediated signaling on activation, death and
migration of macrophages, monocytes and dendritic cells during acute and
chronic infection with Plasmodium chabaudi AS. Methods: Six- to eight-weekold
C57BL/6 and P2X7R -/- male mice received an intraperitoneal inoculation of
10 6 P. chabaudi infected red blood cells (iRBC) and pathological parameters
were obtained before infection and daily after infection. Kinetics of phagocytic
cells in the spleen of these infected animals was determined by flow cytometry,
in relation to number of cells and cell death. Results: Between days 9 and 17
post-infection, 80% of P2X7R -/- mice died, while the C57BL/6 group presented
no death. The parasitemia peak of P2X7R -/- group occurred at day 8 and
C57BL/6 mice presented the peak at day 7. Pathological parameters as weight
change and body temperature were also delayed in knockout mice in
comparison to wild-type (WT) group, and animals showed a late improvement in
clinical conditions. Regarding kinetics, P2X7R -/- mice showed a higher number
of CD11b + cells (20.4 x 10 6 cells) at day 7 post-infection compared to the WT
mice (10.9 x 10 6 cells). In addition, the percentage of leukocytes cell death
found in spleen in the same day was lower in knockout group (12.65%)
compared to C57BL/6 mice (21.25%). Conclusion: Mice lacking the P2X7R
seem to be more susceptible to the exacerbated immune response that is
responsible for clinical symptoms, thus, presenting more severe pathological
parameters for more time. The elevated number of phagocytes in spleen from
P2X7R -/- mice when compared to C57BL/6 mice could be due to the reduced
rate of cell death found in the same spleen.
Financial support: FAPESP