title: Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil.
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: São Luís, Cedral and Buriticupu, Maranhão 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-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-β 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.
authors.affiliation: Programa de Pós- graduação em Ciências da Saúde, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil.|Laboratório de Imunofisiologia, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil.
authors.forename: Bruno de Paulo
authors.initials: Bde P
authors.lastname: Ribeiro
authors.affiliation: Centro de Investigação de Microrganismos, Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil.
authors.forename: Gustavo Capatti
authors.initials: GC
authors.lastname: Cassiano
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil.|Centro Multidisciplinar, Campus Floresta (Universidade Federal do Acre), Cruzeiro do Sul, Acre, Brazil.
authors.forename: Rodrigo Medeiros
authors.initials: RM
authors.lastname: de Souza
authors.affiliation: Laboratório de Imunofisiologia, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil.
authors.forename: Dalila Nunes
authors.initials: DN
authors.lastname: Cysne
authors.affiliation: Laboratório de Imunologia das Parasitoses (Universidade CEUMA), São Luís, Maranhão, Brazil.
authors.forename: Marcos Augusto Grigolin
authors.initials: MA
authors.lastname: Grisotto
authors.affiliation: Laboratório de Imunofisiologia, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil.
authors.forename: Ana Paula Silva
authors.initials: AP
authors.lastname: de Azevedo dos Santos
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil.
authors.forename: Cláudio Romero Farias
authors.initials: CR
authors.lastname: Marinho
authors.affiliation: Laboratório de Pesquisa Básica em Malária (Instituto Evandro Chagas / Secretaria de Vigilância em Saúde / Ministério da Saúde-IEC/SVS/MS), Belém, Pará, Brazil.
authors.forename: Ricardo Luiz Dantas
authors.initials: RL
authors.lastname: Machado
authors.affiliation: Laboratório de Imunofisiologia, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil.
authors.forename: Flávia Raquel Fernandes
authors.initials: FR
authors.lastname: Nascimento
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001938:Brazil / Q000453:epidemiology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002947:Cities / Q000453:epidemiology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D059208:Parasite Load; D010966:Plasmodium vivax / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan