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

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LYMPHOCYTIC APOPTOSIS IN HUMAN P. FALCIPARUM AND P. VIVAX MALÁRIA:<br />

RELATIONSHIP WITH IMUNE RESPONSE TO THE PARASITES<br />

EVELYN KETY PRATT RICCIO 1 ; PAULO RENATO RIVAS TOTINO 1 ; VÍTOR ENNES<br />

VIDAL 2 ; IRENE DA SILVA SOARES 3 ; MAURÍCIO MARTINS RODRIGUES 4 ; JOSÉ<br />

MARIA DE SOUZA 5 ; LILIAN ROSE PRATT-RICCIO 1 ; RENATO PORROZZI DE<br />

ALMEIDA 6 ; MARIA DA GLÓRIA BONECINI DE ALMEIDA 7 ; GRAZIELA MARIA<br />

ZANINI 8 ; CLÁUDIO TADEU DANIEL RIBEIRO 1 ; MARIA DE FÁTIMA FERREIRA DA<br />

CRUZ 1 .<br />

1 Laboratory <strong>of</strong> Malaria Research, Fiocruz, 2 Laboratory <strong>of</strong> Molecular Biology <strong>and</strong><br />

Endemic Disease, Fiocruz, 3 Department <strong>of</strong> Clinical Analyses <strong>and</strong> Toxicology, University<br />

<strong>of</strong> São Paulo, 4 Department <strong>of</strong> Microbiology, Immunology <strong>and</strong> Parasitology, Federal<br />

University <strong>of</strong> São Paulo, 5 Ambulatory <strong>and</strong> Laboratory <strong>of</strong> Malaria Clinical Assays,<br />

Instituto Ev<strong>and</strong>ro Chagas,<br />

6<br />

Laboratory <strong>of</strong> Leishmaniasis Research,<br />

Fiocruz, 7 Immunology Service <strong>of</strong> Ev<strong>and</strong>ro Chagas Clinical Research Institute, Fiocruz<br />

<strong>and</strong> 8 Parasitology Service, Ev<strong>and</strong>ro Chagas Clinical Research Institute, Fiocruz.<br />

INTRODUCTION: Infection with Plasmodium is characterized by both activation <strong>and</strong><br />

suppression <strong>of</strong> the immune system during the course <strong>of</strong> the disease. As apoptosis is an<br />

important mechanism regulating the activation <strong>of</strong> lymphocytes, we decided to study the<br />

role <strong>of</strong> lymphocytic apoptosis during a non complicated malaria attack.<br />

METHODOLOGY: Blood samples were collected from 35 individuals living in malaria<br />

endemic area with positive blood smears, as well as from 17 individuals without<br />

previous reported malaria episodes. Apoptosis in T <strong>and</strong> B cells were analyzed ex–vivo<br />

<strong>and</strong> after 96 hour-culture. Cellular <strong>and</strong> humoral immune responses after antigenic<br />

stimulation, absolute numbers <strong>of</strong> T <strong>and</strong> B cells, B cells polyclonal activation <strong>and</strong> the<br />

auto-immune response against components <strong>of</strong> erythrocytes membrane, cardiolipin,<br />

actin <strong>and</strong> DNA were also investigated. RESULTS: In ex-vivo analyses low levels <strong>of</strong><br />

apoptosis <strong>and</strong> high levels <strong>of</strong> cellular activation in CD4 + cells were observed in malaria<br />

patients, although increased levels <strong>of</strong> early apoptosis in CD4 + <strong>and</strong> CD8 + cells had been<br />

detected. High levels <strong>of</strong> IFN- <strong>and</strong> IL-10 <strong>and</strong> low levels <strong>of</strong> TNF were also verified in<br />

malaria patients. No difference was observed between TNF <strong>and</strong> IL-10 plasmatic levels<br />

between P. vivax <strong>and</strong> P. falciparum infections, although high levels <strong>of</strong> IFN- was<br />

registered in P. vivax malaria patients. No relationship was observed between cytokines<br />

levels <strong>and</strong> activation, viability or PBMC apoptosis. After 96 hour-culture, apoptosis<br />

levels in malaria patients were increased in CD4 + , CD8 + <strong>and</strong> B cells, <strong>and</strong> even in the<br />

presence <strong>of</strong> stimuli the cellular proliferation was lower than in healthy individuals.<br />

Antibodies against membrane erythrocyte components, cardiolipin <strong>and</strong> DNA were<br />

similarly detected in malaria patients <strong>and</strong> healthy individuals, while antibodies against

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