Black S J, Mansfield J M
Department of Veterinary and Animal Sciences, University of Massachusetts-Amherst, Amherst, MA, USA.
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Parasite Immunol. 2016 Dec;38(12):735-743. doi: 10.1111/pim.12387.
African trypanosomes cause human and animal African trypanosomiases, which are chronic, debilitating and often fatal diseases of people and livestock in sub-Saharan Africa. The extracellular protozoan parasites are exemplars of antigenic variation. They direct host-protective B-cell and T-cell immune responses towards hypervariable components of their variable surface glycoprotein coat and evade immune elimination by generating new surface coat antigenic variants at a rate that supersedes immune destruction. This results in recurring waves of parasitemia, tissue invasion and escalating immunopathology in trypanosomiasis-susceptible hosts. Here, we discuss the possibility that host control of African trypanosomes might be improved by immunization with conserved VSG peptides and invariant surface glycoproteins. Infection-induced T-cell recall responses to these typically poorly expressed or nonimmunogenic parasite components induce tissue phagocytes to produce microbicidal materials that kill trypanosomes. Preliminary data that support this immune-enhancing vaccine strategy are discussed, as are host and parasite interactions that might downregulate the protective responses. These include infection-induced immunosuppression and increasing virulence of infecting parasites over time.
非洲锥虫引发人类和动物的非洲锥虫病，这些疾病是撒哈拉以南非洲地区人和牲畜的慢性、使人衰弱且往往致命的疾病。这种细胞外原生动物寄生虫是抗原变异的典型例子。它们将宿主保护性B细胞和T细胞免疫反应导向其可变表面糖蛋白外衣的高变成分，并通过以超过免疫破坏速度产生新的表面外衣抗原变体来逃避免疫清除。这导致锥虫病易感宿主中反复出现寄生虫血症、组织侵袭和不断升级的免疫病理反应。在此，我们讨论通过用保守的VSG肽和不变表面糖蛋白进行免疫接种来改善宿主对非洲锥虫控制的可能性。感染诱导的对这些通常表达不佳或无免疫原性的寄生虫成分的T细胞回忆反应会诱导组织吞噬细胞产生杀灭锥虫的杀菌物质。文中讨论了支持这种免疫增强疫苗策略的初步数据，以及可能下调保护性反应的宿主与寄生虫相互作用。这些相互作用包括感染诱导的免疫抑制以及随着时间推移感染寄生虫毒力的增加。
