Goncalves Ricardo, Christensen Stephen M, Mosser David M
Department of General Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, United States.
Cytokine X. 2020 Oct 31;2(4):100046. doi: 10.1016/j.cytox.2020.100046. eCollection 2020 Dec.
Leishmaniasis can present as a "spectrum" of clinical outcomes. There is evidence that these divergent clinical outcomes are attributable to genetic differences in the human host [1] as well the species of infecting parasite [2]. The spectrum of disease has largely been described by defining the polar opposites of T cell immune responses. In the mouse model, a T1 immune response is associated with low numbers of parasites in lesions, whereas a T2 immune response has been associated with unrestricted parasite growth. In the present work, we revisit leishmaniasis and seek to better define the clinical spectrum as a function of divergent humoral immune responses. We describe examples in human, canine, and even some murine models of leishmaniasis that reveal a direct correlation between high anti-parasite antibody responses and unrestricted parasite growth. Therefore, we propose that the spectral nature of this disease may be due to quantitative and qualitative differences in the antibodies that are produced during disease. In human visceral leishmaniasis, a decrease in anti-parasite antibody levels may actually predict disease resolution. Thus, rather than defining this disease as a simple T1/T2 dichotomy, we propose that clinical leishmaniasis depends on the degree of humoral immunity, with high IgG predicting parasite persistence. These observations have obvious implications for vaccine development in leishmaniasis, and they may extend to other diseases caused by intracellular pathogens.
利什曼病可表现为一系列临床结果。有证据表明，这些不同的临床结果归因于人类宿主的基因差异[1]以及感染寄生虫的种类[2]。疾病的范围很大程度上是通过定义T细胞免疫反应的两个极端来描述的。在小鼠模型中，T1免疫反应与病变中寄生虫数量少有关，而T2免疫反应与寄生虫不受限制的生长有关。在本研究中，我们重新审视利什曼病，并试图根据不同的体液免疫反应更好地定义临床范围。我们在人类、犬类甚至一些利什曼病小鼠模型中描述了一些例子，这些例子揭示了高抗寄生虫抗体反应与寄生虫不受限制的生长之间的直接相关性。因此，我们提出这种疾病的范围性质可能是由于疾病期间产生的抗体在数量和质量上的差异。在人类内脏利什曼病中，抗寄生虫抗体水平的降低实际上可能预示着疾病的缓解。因此，我们不是将这种疾病定义为简单的T1/T2二分法，而是提出临床利什曼病取决于体液免疫的程度，高IgG预示着寄生虫的持续存在。这些观察结果对利什曼病疫苗的开发具有明显的意义，并且可能扩展到由细胞内病原体引起的其他疾病。
