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

REGULATION OF IMMUNE RESPONSE AGAINST PLASMODIUM
BERGHEI ANKA INFECTION IS DEPENDENT OF SUPPRESSOR OF
SIGNALING CYTOKINES 2 (SOCS2) PATHWAY
FATIMA BRANT (PG) (1,3#) , ALINE SILVA MIRANDA (PG) (1,3#) , LISIA ESPER
(PG) (1,3) , RONAN RICARDO SABINO ARAÚJO (PG) (1) , ANDREIA BARROSO
(IC) (1) , CYNTHIA HONORATO VAL (PG) (1) , BRUNO CABRAL OLIVEIRA
(PG) (1) , FREDERICO MARIANETTI SORIANI (PhD) (1) , MILENE ALVARENGA
RACHID (PhD) (2) , HERBERT BERNARD TANOWITZ (PhD) (4) , ANTÔNIO
LUCIO TEIXEIRA (PhD) (1,3) , FABIANA SIMÃO MACHADO (PhD) (1,3)
Instituto de Ciências Biológicas, Departamentos de Bioquímica e Imunologia 1 e
Patologia 2 , Faculdade de Medicina, Departamento de Clínica Médica 3 ,
Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil. Albert
Einstein College of Medicine, Department of Pathology 4 , Bronx, New York,
USA. # Equal contribution.
Introduction: The cerebral malaria (CM) is the most severe neurological
complication and one of the most life-threatening occurring from Plasmodium
falciparum infection. Mice infected with P. berghei ANKA (PbA) faithfully
recapitulate many of the characteristics of human CM and it has been an
important tool to investigate the disease pathogenesis. Cerebral malaria (CM)
is a complex condition whose pathogenesis is still poorly understood, it likely
involves deregulation of inflammatory response and alterations in
neurotransmitters. The suppressor of cytokine signaling (SOCS) 2 is an
intracellular protein induced by eicosanoids and hormones, and is important to
modulate the inflammatory response. Recent studies suggest a role for SOCS-
2 in neural development, growth, neurogenesis and stem cell differentiation.
However, the involvement of SOCS2 in CM is not known.
Method: C57Bl/6(WT) and SOCS2 -/- mice were infected with PbA and the
parasitemia, survival and body weight were monitored periodically. The
production of cytokines (TNF-α, IL-1β, TGF- β, IL-6, IFN-γ, IL-12 and IL-10) in
the brain and spleen was assessed by ELISA and flow cytometry. The
expression of SOCS1 and SOCS3 was assessed by RT-PCR. Leukocyte
recruitment in the brain was evaluated by intravital microscopy. Nitric oxide
(NO) was assessed by the Griess method in the brain. Histopathological
analysis was performed in brain.
Results: The parasitemia was significantly lower in SOCS2 -/- compared with
WT mice and no difference in lost weight was detected among the groups. In
the brain of PbA-infected SOCS2 -/- mice there was a significant increased
expression of TGF-β and IL-17 and increased level of NO when compared with
infected WT mice. Additionally, there was a decreased expression in the brain
but not spleen of IL-1β, TNF-α, IL-10 and IL-12 of infected SOCS2 -/- mice when