Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

Author(s)

Ribeiro, Bruno de Paulo ^{[1, 2]} ; Cassiano, Gustavo Capatti ^[3] ; de Souza, Rodrigo Medeiros ^{[4, 5]} ; Cysne, Dalila Nunes ^[1] ; Grigolin Grisotto, Marcos Augusto ^[6] ; Silva de Azevedo dos Santos, Ana Paula ^[1] ; Farias Marinho, Claudio Romero ^[4] ; Dantas Machado, Ricardo Luiz ^[7] ; Fernandes Nascimento, Flavia Raquel ^[1]

Affiliation

^[1] Univ Fed Maranhao UFMA, Lab Imunofisiol, Sao Luis, Maranhao - Brazil

^[2] Univ Fed Maranhao UFMA, Programa Posgrad Ciencias Saude, Sao Luis, Maranhao - Brazil

^[3] Fac Med Sao Jose do Rio Preto FAMERP, Ctr Invest Microrganismos, Sao Jose Do Rio Preto, SP - Brazil

^[4] Univ Sao Paulo ICB USP, Dept Parasitol, Sao Paulo, SP - Brazil

^[5] Univ Fed Acre, Ctr Multidisciplinar, Campus Floresta, Cruzeiro Do Sul, Acre - Brazil

^[6] Univ CEUMA, Lab Imunol Parasitoses, Sao Luis, Maranhao - Brazil

^[7] Minist Saude IEC SVS MS, Secretaria Vigilancia Saude, Inst Evandro Chagas, Lab Pesquisa Basica Malaria, Belem, Para - Brazil

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 10, n. 3 MAR 2016.
• Web of Science Citations: 6

Abstract

Mechanisms involved in severe P. vivax malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: Sao Luis, Cedral and Buriticupu, Maranhao state, Brazil, areas of high prevalence of P. vivax. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-alpha, interferon gamma (IFN-gamma and transforming growth factor beta (TGF-beta were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and P. vivax-like CSP variants. Patients infected with P. vivax showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection. (AU)

• FAPESP's process: 09/53889-0 - Study of the immunopathological mechanisms involved in pregnancy-associated malaria
• Grantee: Cláudio Romero Farias Marinho
• Support Opportunities: Research Grants - Young Investigators Grants