Dynamics and kinetics of natural killer cell cytotoxicity in human malaria as evaluated by a novel stepwise cytotoxicity assay

Abstract

Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process. Key-words: Malaria. Plasmodium vivax. Plasmodium falciparum. Natural killer cells. Cytotoxicity. RESUMOA malária causa importantes alterações do sistema imunitário, muitas ainda mal definidas. Para permitir uma avaliação abrangente da atividade citotóxica das células natural killer em pacientes com malária, desenvolvemos um teste capaz de avaliar concomitantemente a dinâmica e a cinética do processo. Para a avaliação da cinética, células mononucleares do sangue periférico interagiram com células K562 e foram mantidas em agarose, enquanto para avaliar a dinâmica as células eram mantidas em suspensão. A cinética da atividade citotóxica das células NK foi mais rápida em pacientes com Plasmodium vivax, do que naqueles infectados com P. falciparum. Nestes, houve correlação positiva entre a atividade citotóxica das células NK e a parasitemia. O padrão da dinâmica da atividade citotóxica nos pacientes com malária foi bem diferente daquele apresentado pelos indivíduos sadios. Enquanto nestes, a atividade estava muito aumentada no início da incubação das células, sofrendo posteriormente uma redução, nos indivíduos infectados foram detectados sucessivos picos de atividade citotóxica. Nossos resultados confirmam a ocorrência de alteração funcional das células NK na malária humana e acrescentam novos dados sobre a dinâmica e a cinética da atividade citotóxica. Palavras-chaves: Malária. Plasmodium vivax. Plasmodium falciparum. Células natural killer. Citotoxicidade. Plasmodium infection causes an extensive alteration of the immune response of the host, characterized by polyclonal activation of B lymphocytes, production of autoantibodies, increased levels of several cytokines, and activation of lymphocytes and macrophages, which lead to immunodeficiency and autoimmunity 1 9 16 23 . A less known component of the immune system that also present functional alterations during malaria infection are natural killer cells 21 25 . These cells comprise about 10-15% of all circulating lymphocytes in humans and...

High IFN-gamma and TNF production by peripheral NK cells of Colombian patients with different clinical presentation of Plasmodium falciparum

“…The increased of the NK population proportions during acute and, probably, during severe malaria described in this study, in addition to a positive correlation between NK cytotoxicity and levels of parasitaemia reported by other authors in patients infected with P. falciparum [32], confirms the induction of robust cellular responses to P. falciparum in naturally infected individuals form the American continent, and highlights the importance of further exploring the role of these cells and theirs subsets in the immunopathology during severe malaria outside Africa.…”

“…Studies on the dynamics of NK activity in malaria patients revealed heterogeneous results, particularly in P. falciparum infected individuals. Nevertheless, confirmation of NK activation has been observed in subjects with Plasmodium vivax or P. falciparum infection [32]. …”

Profile of Natural Killer (NK) Cells in Simple Malaria in Adults

“…There is little data in the literature related to a decline in NK cells activity in uncomplicated malaria. However, Ribero-Dias and coll [14] denounced an alteration of the cytotoxic function of NK cells during Plasmodium falciparum malaria. In another context of a murine model, Dogruman and coll [15] reported lower expression of NK markers in P. berghei infected mice than in healthy witnesses.…”