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

Malaria Journal

Research

Dhelio Batista Pereira¹  Mauro Shugiro Tada¹  Tiago Antônio de Oliveira Mendes²  Fernanda Sumika Hojo de Souza³  Lilian Lacerda Bueno⁴  Natália Satchiko Hojo-Souza⁴  Mariana Santos Cardoso⁴  Ricardo Toshio Fujiwara⁴  Daniella Castanheira Bartholomeu⁴  Graziela Maria Zanini⁵ 

[1] Centro de Pesquisa em Medicina Tropical, Porto, Velho, Rondônia, Brazil;Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;Departamento de Ciência da Computação, Universidade Federal de São João del-Rei, São João del-Rei, Minas Gerais, Brazil;Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil;

关键词: Plasmodium vivax;    Malaria;    Cytokines;    Chemokines;   

DOI  :  10.1186/s12936-017-1683-5

 received in 2016-11-08, accepted in 2017-01-05,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2017