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

Autor: Marcos Augusto Grigolin Grisotto, Flávia R.F. Nascimento, Ricardo Luiz Dantas Machado, Gustavo Capatti Cassiano, Dalila Nunes Cysne, Claudio Romero Farias Marinho, Rodrigo Medeiros de Souza, Bruno de Paulo Ribeiro, Ana Paula Silva de Azevedo dos Santos
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Plasmodium
Physiology
medicine.medical_treatment
Plasmodium vivax
Protozoan Proteins
Pathology and Laboratory Medicine
Parasite load
Parasite Load
Polimorfismo Gen?tico
0302 clinical medicine
Immune Physiology
Medicine and Health Sciences
Parasite hosting
Interferon gamma
Child
MALÁRIA
Immune Response
Cells
Cultured
Protozoans
Innate Immune System
biology
lcsh:Public aspects of medicine
Malarial Parasites
Interleukin
Citocinas
Middle Aged
Circumsporozoite protein
Infectious Diseases
Cytokine
Child
Preschool
Cytokines
Female
Brazil
Research Article
medicine.drug
Adult
lcsh:Arctic medicine. Tropical medicine
Adolescent
lcsh:RC955-962
Immunology
030231 tropical medicine
Plasmodium vivax / gen?tica
Peripheral blood mononuclear cell
Parasite Replication
Polimorfismo de Fragmento de Restri??o
Gen?tipo
Young Adult
03 medical and health sciences
Signs and Symptoms
Parasite Groups
parasitic diseases
Malaria
Vivax
Parasitic Diseases
medicine
Animals
Humans
Cities
Plasmodium vivax / imunologia
Varia??o Gen?tica
Inflammation
Interleukins
Organisms
Public Health
Environmental and Occupational Health
Genetic Variation
Biology and Life Sciences
lcsh:RA1-1270
Molecular Development
Tropical Diseases
biology.organism_classification
Virology
Parasitic Protozoans
Malaria
Cross-Sectional Studies
030104 developmental biology
Immune System
Leukocytes
Mononuclear
Parasitology
Apicomplexa
Mal?ria Vivax / parasitologia
Developmental Biology
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
PLoS Neglected Tropical Diseases
Repositório Digital do Instituto Evandro Chagas (Patuá)
Instituto Evandro Chagas (IEC)
instacron:IEC
PLoS Neglected Tropical Diseases, Vol 10, Iss 3, p e0004479 (2016)
ISSN: 1935-2735
Popis: 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.
Author Summary Recent evidences have associated P. vivax infections with clinical complications, previously only attributed to P. falciparum malaria. The interaction between host and parasite may contribute to severity of the disease, however, the specific contribution of each factor remains unclear. Previous studies have shown that polymorphisms in Plasmodium vivax CSP may interfere in systemic reactions, response to drug treatments, leading to different symptoms as well as humoral responses. In this study, we investigate whether these polymorphisms could influence the parasite load and cytokine profile, which altogether may influence the malaria outcome. In this sense, studies have shown that subjects with high parasitic loads, responding with production of pro-inflammatory cytokines develop a more severe disease. The present data indicate that VK247 variant are associated with significant higher parasite loads and pro-inflammatory cytokine profile compared to VK210 variant. In this regard, this study demonstrates that P. vivax CSP polymorphisms have systemic effects in the host immune response, and the investigation of immunogenicity of parasite proteins may provide evidences for a better understanding of this infection.
Databáze: OpenAIRE
Externí odkaz: