| Autor: |
Ribeiro Bde P; 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., Cassiano GC; Centro de Investigação de Microrganismos, Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil., de Souza RM; 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., Cysne DN; Laboratório de Imunofisiologia, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil., Grisotto MA; Laboratório de Imunologia das Parasitoses (Universidade CEUMA), São Luís, Maranhão, Brazil., de Azevedo dos Santos AP; Laboratório de Imunofisiologia, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil., Marinho CR; Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil., Machado RL; Laboratório de Pesquisa Básica em Malária (Instituto Evandro Chagas / Secretaria de Vigilância em Saúde / Ministério da Saúde-IEC/SVS/MS), Belém, Pará, Brazil., Nascimento FR; Laboratório de Imunofisiologia, Universidade Federal do Maranhão (UFMA), São Luís, Maranhão, Brazil. |
| Abstrakt: |
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. |
