Lima-Junior Josué da Costa, Pratt-Riccio Lilian Rose
Laboratory of Immunoparasitology, Oswaldo Cruz Institute - Fiocruz , Rio de Janeiro , Brazil.
Laboratory of Malaria Research, Oswaldo Cruz Institute - Fiocruz , Rio de Janeiro , Brazil.
Front Immunol. 2016 Jan 27;7:13. doi: 10.3389/fimmu.2016.00013. eCollection 2016.
The importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. Nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. Susceptibility to malaria depends on exposure profile, epidemiological characteristics, and several components of the innate and adaptive immune system that influences the quality of the immune response generated during the Plasmodium lifecycle in the vertebrate host. But it is well known that the parasite's enormous capacity of genetic variation in conjunction with the host genetics polymorphism is also associated with a wide spectrum of susceptibility degrees to complicated or severe forms of the disease. In this scenario, variations in genes of the major histocompatibility complex (MHC) associated with host resistance or susceptibility to malaria have been identified and used as markers in host-pathogen interaction studies, mainly those evaluating the impact on the immune response, acquisition of resistance, or increased susceptibility to infection or vulnerability to disease. However, due to the intense selective pressure, number of cases, and mortality rates, the majority of the reported associations reported concerned Plasmodium falciparum malaria. Studies on the MHC polymorphism and its association with Plasmodium vivax, which is the most widespread Plasmodium and the most prevalent species outside the African continent, are less frequent but equally important. Despite punctual contributions, there are accumulated evidences of human genetic control in P. vivax infection and disease. Herein, we review the current knowledge in the field of MHC and derived molecules (HLA Class I, Class II, TNF-α, LTA, BAT1, and CTL4) regarding P. vivax malaria. We discuss particularly the results of P. vivax studies on HLA class I and II polymorphisms in relation to host susceptibility, naturally acquired immune response against specific antigens and the implication of this knowledge to overcome the parasite immune evasion. Finally, the potential impact of such polymorphisms on the development of vaccine candidate antigens against P. vivax will be studied.
自上世纪中叶以来，人们一直在研究宿主和寄生虫遗传因素在疟疾抗性或易感性中的重要性。如今，在所有影响人类的疾病中，疟疾对人类基因组的选择性压力仍然处于最高水平之一。对疟疾的易感性取决于暴露情况、流行病学特征以及先天性和适应性免疫系统的几个组成部分，这些因素会影响疟原虫在脊椎动物宿主体内生命周期中产生的免疫反应质量。但众所周知，寄生虫巨大的遗传变异能力与宿主基因多态性相结合，也与对复杂或严重形式疾病的广泛易感性程度相关。在这种情况下，已确定主要组织相容性复合体（MHC）相关基因的变异与宿主对疟疾的抗性或易感性有关，并将其用作宿主-病原体相互作用研究中的标记物，主要用于评估对免疫反应、抗性获得或感染易感性增加或疾病易感性的影响。然而，由于强烈的选择压力、病例数量和死亡率，大多数报道的关联都与恶性疟原虫疟疾有关。对间日疟原虫（这是分布最广的疟原虫，也是非洲大陆以外最普遍的物种）的MHC多态性及其关联的研究较少，但同样重要。尽管有一些零星的贡献，但有越来越多的证据表明人类基因对间日疟原虫感染和疾病有控制作用。在此，我们综述了关于间日疟原虫疟疾的MHC及其衍生分子（HLA I类、II类、TNF-α、LTA、BAT1和CTL4）领域的现有知识。我们特别讨论了间日疟原虫关于HLA I类和II类多态性与宿主易感性、针对特定抗原的自然获得性免疫反应以及这些知识对克服寄生虫免疫逃逸的意义的研究结果。最后，将研究这种多态性对间日疟原虫疫苗候选抗原开发的潜在影响。
