Abstract
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.ResultsPlasmodium 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.
Highlights
The clinical outcome of malaria depends on the delicate balance between pro-inflammatory and immunomodulatory cytokine responses triggered during infection
Plasmodium vivax infection triggers a marked pro‐inflammatory cytokine response The circulating levels of pro-inflammatory cytokines such as IL-6, IL-17, IL-12p40, and TNF were prominent in P. vivax naturally infected individuals when compared to plasma levels observed in other groups (Fig. 1a–d), significant differences to control groups were observed only for IL-6 and IL-17 (p < 0.0001 and p = 0.0051, respectively) (Fig. 1a, b)
The P. vivax infection resulted in a significant reduction of IFN-γ plasma levels when compared to control groups (p < 0.0001) (Fig. 1e), with circulating levels of IFN-γ detected in only 20% of the samples from P. vivax group
Summary
The clinical outcome of malaria depends on the delicate balance between pro-inflammatory and immunomodulatory cytokine responses triggered during infection. 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. Malaria is a complex disease involving genetic factors inherent to the parasite and to the host, geographical and environmental aspects that favour its occurrence and the difficulty of its eradication [2]. During infection, both the antibody-mediated and the cell-mediated immunity play an important role for achieving clinical immunity [3]. The fine-tuning between inflammatory and anti-inflammatory response appears to be a determinant factor in the clinical outcome of the disease [3,4,5]
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