Analysis of lymphocytes in patients with Plasmodium vivax malaria and its relation to the annexin-A1 and IL-10

Borges, Quessi Irias; Fontes, Cor Jésus Fernandes; Damazo, Amílcar Sabino

doi:10.1186/1475-2875-12-455

Cited by 14 publications

(20 citation statements)

References 44 publications

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“…In the present study, vivax malaria patients have shown significant low RANTES/CCL5 levels, but just weakly associated with IL-6, IL-12p40, IFN-γ or MCP-1/CCL2. The lower levels of RANTES/CCL5 could be explained by the CD8 + T cells reduction [43–45] and thrombocytopaenia [8, 10, 11, 44–46] observed during vivax malaria. A study carried out with children infected with P. falciparum observed an association between thrombocytopaenia and lower RANTES plasma levels [47].…”

Section: Discussionmentioning

confidence: 99%

On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

Hojo-Souza

Pereira

Souza

et al. 2017

Malar J

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BackgroundThe clinical outcome of malaria depends on the delicate balance between pro-inflammatory and immunomodulatory cytokine responses triggered during infection. Despite the numerous reports on characterization of plasma levels of cytokines/chemokines, there is no consensus on the profile of these mediators during blood stage malaria. The identification of acute phase biomarkers might contribute to a better understanding of the disease, allowing the use of more effective therapeutic approaches to prevent the progression towards severe disease. In the present study, the plasma levels of cytokines and chemokines and their association with parasitaemia and number of previous malaria episodes were evaluated in Plasmodium vivax-infected patients during acute and convalescence phase, as well as in healthy donors.MethodsSamples of plasma were obtained from peripheral blood samples from four different groups: P. vivax-infected, P. vivax-treated, endemic control and malaria-naïve control. The cytokine (IL-6, IL-10, IL-17, IL-27, TGF-β, IFN-γ and TNF) and chemokine (MCP-1/CCL2, IP-10/CXCL10 and RANTES/CCL5) plasma levels were measured by CBA or ELISA. The network analysis was performed using Spearman correlation coefficient.Results Plasmodium vivax infection induced a pro-inflammatory response driven by IL-6 and IL-17 associated with an immunomodulatory profile mediated by IL-10 and TGF-β. In addition, a reduction was observed of IFN-γ plasma levels in P. vivax group. A lower level of IL-27 was observed in endemic control group in comparison to malaria-naïve control group. No significant results were found for IL-12p40 and TNF. It was also observed that P. vivax infection promoted higher levels of MCP-1/CCL2 and IP-10/CXCL10 and lower levels of RANTES/CCL5. The plasma level of IL-10 was elevated in patients with high parasitaemia and with more than five previous malaria episodes. Furthermore, association profile between cytokine and chemokine levels were observed by correlation network analysis indicating signature patterns associated with different parasitaemia levels.ConclusionsThe P. vivax infection triggers a balanced immune response mediated by IL-6 and MCP-1/CCL2, which is modulated by IL-10. In addition, the results indicated that IL-10 plasma levels are influenced by parasitaemia and number of previous malaria episodes.

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Section: Discussionmentioning

confidence: 99%

On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

Hojo-Souza

Pereira

Souza

et al. 2017

Malar J

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“…Several studies have shown that there is a reduction in the percentage and/or absolute number of CD8 + T cells in the peripheral blood during acute P. falciparum or P. vivax infection [ 10 - 14 ], and these reductions have been attributed to the apoptosis of these cells [ 15 , 16 ], the reallocation of T cells to sites of inflammation [ 12 , 17 ] or other factors such as the suppression of CD8 + T cells induced by sporozoites or infected red blood cells [ 18 ]. In regard to P. vivax infection, however, reports have shown that there is no significant difference in the percentage of CD8 + T cells during an acute malaria infection compared with that in uninfected individuals [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Phenotypic profiling of CD8+ T cells during Plasmodium vivax blood-stage infection

Hojo-Souza

Pereira²,

Passos

et al. 2015

BMC Infect Dis

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BackgroundFor a long time, the role of CD8+ T cells in blood-stage malaria was not considered important because erythrocytes do not express major histocompatibility complex (MHC) class I proteins. While recent evidences suggest that CD8+ T cells may play an important role during the erythrocytic phase of infection by eliminating parasites, CD8+ T cells might also contribute to modulate the host response through production of regulatory cytokines. Thus, the role of CD8+ T cells during blood-stage malaria is unclear. Here, we report the phenotypic profiling of CD8+ T cells subsets from patients with uncomplicated symptomatic P. vivax malaria.MethodsBlood samples were collected from 20 Plasmodium vivax-infected individuals and 12 healthy individuals. Immunophenotyping was conducted by flow cytometry. Plasma levels of IFN-γ, TNF-α and IL-10 were determined by ELISA/CBA. Unpaired t-test or Mann–Whitney test was used depending on the data distribution.ResultsP. vivax-infected subjects had lower percentages and absolute numbers of CD8+CD45RA+ and CD8+CD45RO+ T cells when compared to uninfected individuals (p ≤ 0.0002). A significantly lower absolute number of circulating CD8+CD45+CCR7+ cells (p = 0.002) was observed in P. vivax-infected individuals indicating that infection reduces the number of central memory T cells. Cytokine expression was significantly reduced in the naïve T cells from infected individuals compared with negative controls, as shown by lower numbers of IFN-γ+ (p = 0.001), TNF-α+ (p < 0.0001) and IL-10+ (p < 0.0001) CD8+ T cells. Despite the reduction in the number of CD8+ memory T cells producing IFN-γ (p < 0.0001), P. vivax-infected individuals demonstrated a significant increase in memory CD8+TNF-α+ (p = 0.016) and CD8+IL-10+ (p = 0.004) cells. Positive correlations were observed between absolute numbers of CD8+IL-10+ and numbers of CD8+IFN-γ+ (p < 0.001) and CD8+TNF-α+ T cells (p ≤ 0.0001). Finally, an increase in the plasma levels of TNF-α (p = 0.017) and IL-10 (p = 0.006) and a decrease in the IFN-γ plasma level (p <0.0001) were observed in the P. vivax-infected individuals.ConclusionsP. vivax infection reduces the numbers of different subsets of CD8+ T cells, particularly the memory cells, during blood-stage of infection and enhances the number of CD8+ memory T cells expressing IL-10, which positively correlates with the number of cells expressing TNF-α and IFN-γ.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0762-x) contains supplementary material, which is available to authorized users.

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“…Interestingly, in patients infected with Plasmodium vivax, AnxA1 expression was increased in regulatory T cells and decreased in CD4 + and CD8 + T cells. Additionally, it has been suggested that AnxA1 may contribute to IL-10 production in plasma of patients with vivax malaria (45). Considering the increase in AnxA1 serum levels in ML patients, our findings suggest that upregulation of AnxA1, similarly to other anti-inflammatory markers (68), is not effective to counterbalance the higher levels of proinflammatory mediators present in ML patients, including higher levels of TNF-a.…”

Section: Discussionmentioning

confidence: 63%

“…AnxA1 expression has been extensively investigated in models of sterile inflammation, leading to the recognition of its role as a key modulator of both of the innate and adaptive immune systems (15,43). However, in the context of intracellular parasite infection only few studies (28,44,45) have been reported, including the demonstration that AnxA1 expression is locally increased in LCL lesions caused by L. braziliensis infection (29). Given that L. braziliensis infection may lead patients to develop an exacerbated inflammatory response, with intense tissue damage in chronic disease stages (3,4,6), the understanding of the mechanisms involved in the modulation of inflammatory responses, including AnxA1 expression, in leishmaniasis may provide new insights for the development of effective therapies.…”

Section: Discussionmentioning

confidence: 99%

Annexin A1 Is Involved in the Resolution of Inflammatory Responses duringLeishmania braziliensisInfection

Oliveira

Testasicca

Vago

et al. 2017

The Journal of Immunology

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Leishmaniases are diseases caused by several species. () can cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated in-infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also after infection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1 mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1 mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-γ, IL-4, and IL-10. AnxA1 mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-κB) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed during infection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size.

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Analysis of lymphocytes in patients with Plasmodium vivax malaria and its relation to the annexin-A1 and IL-10

Cited by 14 publications

References 44 publications

On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

Phenotypic profiling of CD8+ T cells during Plasmodium vivax blood-stage infection

Annexin A1 Is Involved in the Resolution of Inflammatory Responses duringLeishmania braziliensisInfection

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