RESUMO
INTRODUCTION: A proliferation-inducing ligand (APRIL) and B cell activation factor (BAFF) are known to play a significant role in the pathogenesis of several diseases, including BAFF in malaria. The aim of this study was to investigate whether APRIL and BAFF plasma concentrations could be part of inflammatory responses associated with P. vivax and P. falciparum malaria in patients from the Brazilian Amazon. METHODS: Blood samples were obtained from P. vivax and P. falciparum malaria patients (n = 52) resident in Porto Velho before and 15 days after the beginning of treatment and from uninfected individuals (n = 12). We investigated APRIL and BAFF circulating levels and their association with parasitaemia, WBC counts, and cytokine/chemokine plasma levels. The expression levels of transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) on PBMC from a subset of 5 P. vivax-infected patients were analyzed by flow cytometry. RESULTS: APRIL plasma levels were transiently increased during acute P. vivax and P. falciparum infections whereas BAFF levels were only increased during acute P. falciparum malaria. Although P. vivax and P. falciparum malaria patients have similar cytokine profiles during infection, in P. vivax acute phase malaria, APRIL but not BAFF levels correlated positively with IL-1, IL-2, IL-4, IL-6, and IL-13 levels. We did not find any association between P. vivax parasitaemia and APRIL levels, while an inverse correlation was found between P. falciparum parasitaemia and APRIL levels. The percentage of TACI positive CD4+ and CD8+ T cells were increased in the acute phase P. vivax malaria. CONCLUSION: These findings suggest that the APRIL and BAFF inductions reflect different host strategies for controlling infection with each malaria species.
Assuntos
Fator Ativador de Células B/sangue , Malária Falciparum/sangue , Malária Vivax/sangue , Malária/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adulto , Antimaláricos/uso terapêutico , Fator Ativador de Células B/imunologia , Brasil , Estudos de Casos e Controles , Quimioterapia Combinada/métodos , Feminino , Voluntários Saudáveis , Interações Hospedeiro-Parasita/imunologia , Humanos , Interleucinas/sangue , Interleucinas/imunologia , Contagem de Leucócitos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Malária/tratamento farmacológico , Malária/parasitologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Masculino , Parasitemia/imunologia , Parasitemia/parasitologia , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Proteína Transmembrana Ativadora e Interagente do CAML/imunologia , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia , Adulto JovemRESUMO
BACKGROUND: Severe anaemia is a common complication of Plasmodium falciparum malaria in hyperendemic regions. Premature elimination of non-parasitized red blood cells (nRBC) has been considered as one mechanism involved in the genesis of severe malaria anaemia. It has been reported that apoptosis can occur in RBC and, consequently, this cell death process could contribute to anaemia. This study was performed to evaluate the susceptibility of nRBC to apoptosis in a malaria anaemia murine model. METHODS: Balb/c mice were intraperitonially inoculated with 1 × 106 P. yoelii 17XL parasitized RBC (pRBC) and, then, parasitaemia and anaemia were monitored. Apoptosis in both pRBC and nRBC was assessed during early and late phases of infection by flow cytometry using Syto 16 and annexin V-PE double staining and forward scatter measurement. RESULTS: As expected, experimental infection of Balb/c mice with Plasmodium yoelii 17XL parasites was characterized by progressive increase of parasitaemia and acute anaemia, leading to death. Flow cytometry analysis showed that a number of pRBC was in the apoptotic process. It was noteworthy that the increase of nRBC apoptosis levels occurred in the late phase of infection, when anaemia degree was notably accentuated, while no significant alteration was observed in the early phase. CONCLUSION: The increased levels of nRBC apoptosis herein firstly reported, in malaria infection could represent a putative mechanism worsening the severity of malarial anaemia.