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 pa… Show more
“…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.…”
Section: Discussionsupporting
confidence: 82%
“…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]. …”
BackgroundIn Colombia, Plasmodium falciparum infection rarely results in severe disease or mortality compared to infections in African populations. During natural infection NK cells exhibit a cytolytic effect and regulate dendritic cells, macrophages, neutrophils as well as affect antigen specific T and B cell responses. To characterize the NK cells in P. falciparum infected patients of a highly endemic region of Colombia, the degree of NK proliferation and production of IFN gamma and TNF production in these cells were explored.MethodsSeventeen patients with acute and three with severe P. falciparum malaria patients from the Northwest region of the country were recruited in the study. In addition, 20 healthy controls were included: 10 from Medellin (no-transmission area) and 10 from the Uraba region (a malaria endemic area). Immunophenotypic analysis of peripheral mononuclear cells was performed by FACS to detect total number of NK cells, subtypes and intracellular IFNγ and TNF production by NK cells in the different patient groups.ResultsThe total mean CD56+/CD3- NK cell proportions in acute and severe malaria subjects were 9.14% (7.15%CD56dim, 2.01%CD56bright) and 19.62% (16.05%CD56dim, 3.58%CD56bright), respectively, in contrast to healthy controls from endemic (total mean CD56+/CD3-1.2%) and non-endemic area (total mean CD56+/CD3- 0.67%). Analysis of basal IFNγ and TNF levels confirmed the CD56bright NK population as the main cytokine producer (p < 0.0001) in the groups affected with malaria, with the CD56dim NK cell exhibiting the highest potential of TNF production after stimulus in the acute malaria group.ConclusionsThe results confirm the important role of not only CD56bright but also of CD56dim NK cell populations as producers of the two cytokines in malaria patients in Colombia.
“…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.…”
Section: Discussionsupporting
confidence: 82%
“…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]. …”
BackgroundIn Colombia, Plasmodium falciparum infection rarely results in severe disease or mortality compared to infections in African populations. During natural infection NK cells exhibit a cytolytic effect and regulate dendritic cells, macrophages, neutrophils as well as affect antigen specific T and B cell responses. To characterize the NK cells in P. falciparum infected patients of a highly endemic region of Colombia, the degree of NK proliferation and production of IFN gamma and TNF production in these cells were explored.MethodsSeventeen patients with acute and three with severe P. falciparum malaria patients from the Northwest region of the country were recruited in the study. In addition, 20 healthy controls were included: 10 from Medellin (no-transmission area) and 10 from the Uraba region (a malaria endemic area). Immunophenotypic analysis of peripheral mononuclear cells was performed by FACS to detect total number of NK cells, subtypes and intracellular IFNγ and TNF production by NK cells in the different patient groups.ResultsThe total mean CD56+/CD3- NK cell proportions in acute and severe malaria subjects were 9.14% (7.15%CD56dim, 2.01%CD56bright) and 19.62% (16.05%CD56dim, 3.58%CD56bright), respectively, in contrast to healthy controls from endemic (total mean CD56+/CD3-1.2%) and non-endemic area (total mean CD56+/CD3- 0.67%). Analysis of basal IFNγ and TNF levels confirmed the CD56bright NK population as the main cytokine producer (p < 0.0001) in the groups affected with malaria, with the CD56dim NK cell exhibiting the highest potential of TNF production after stimulus in the acute malaria group.ConclusionsThe results confirm the important role of not only CD56bright but also of CD56dim NK cell populations as producers of the two cytokines in malaria patients in Colombia.
“…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.…”
Justification: In the problematic of protection against severe forms of malaria, premunition has often been mentioned as a protective factor acquired in adults at the cost of multiple infections for several years. Exploration of the cellular component of anti-parasite immunity in uncomplicated malaria will provide comparisons of evidence that, despite relative protection, 2 to 3% of adults living in the endemic zone are victims of severe malaria. Main objective: The objective was to evaluate the role of the innate cellular response in susceptibility to uncomplicated malaria in subjects older than 15 years. Patients and Methods: It was a prospective study with descriptive and analytical purpose that took place at Koumassi General Hospital for simple malaria patients and the NBTC for witnesses. All blood samples were analyzed in the Immunology and Hematology Laboratory of CHU de Cocody. It included 50 patients (25 patients with malaria and 25 witnesses) of both sexes, over a 3-month period. The samples carried were processed in the said-laboratory. Results: The average age of our patients was 35 years. The mean of NK cells were 45 cells/mm 3 in patients and 154.64 cells/ mm 3 in witness persons. The risk of not seeing a simple malaria when the number of NK cells is high was 9.03. The PPV was 88.88% and the NPV was 62.6%. The mean parasitemia in patients was 1840 trophozoites/μL. The influence of NK cells on parasitemia was undetermined with a PPV at 1% and a NPV at 39.13%. Conclusion: Susceptibility to simple malaria is a multifactorial phenomenon in which the immune response plays a central role. The evolution towards this clinical state will have to be studied with all the other cellular actors to better appreciate the role of NK cells during its evolution.
Plasmodium vivax infection, the predominant cause of malaria in Asia and Latin America, affects ~14 million individuals annually, with considerable adverse effects on wellbeing and socioeconomic development. A clinical hallmark of Plasmodium infection, the paroxysm, is driven by pyrogenic cytokines produced during the immune response. Here, we review studies on the role of specific immune cell types, cognate innate immune receptors, and inflammatory cytokines on parasite control and disease symptoms. This review also summarizes studies on recurrent infections in individuals living in endemic regions as well as asymptomatic infections, a serious barrier to eliminating this disease. We propose potential mechanisms behind these repeated and subclinical infections, such as poor induction of immunological memory cells and inefficient T effector cells. We address the role of antibody‐mediated resistance to P. vivax infection and discuss current progress in vaccine development. Finally, we review immunoregulatory mechanisms, such as inhibitory receptors, T regulatory cells, and the anti‐inflammatory cytokine, IL‐10, that antagonizes both innate and acquired immune responses, interfering with the development of protective immunity and parasite clearance. These studies provide new insights for the clinical management of symptomatic as well as asymptomatic individuals and the development of an efficacious vaccine for vivax malaria.
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