de Carvalho Renan V H, Lima-Júnior Djalma S, de Oliveira Caroline V, Zamboni Dario S
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto Medical School, FMRP/USP. Av. Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil.
iScience. 2020 Dec 29;24(1):102004. doi: 10.1016/j.isci.2020.102004. eCollection 2021 Jan 22.
New World species of the intracellular protozoan parasites of the genus can cause mucocutaneous leishmaniases. The presence of an endosymbiotic Leishmania RNA virus (LRV) in (.) promotes disease exacerbation and the development of mucocutaneous disease. It was previously reported that LRV blocks the NLRP3 inflammasome, but additional mechanisms remain unclear. Here, we investigated whether LRV interferes with the inflammasome via caspase-11, which induces non-canonical NLRP3 activation and was reported to be activated by . By using macrophages and mice, we found that LRV inhibits caspase-11 activation and IL-1β release by . in a TLR3- and ATG5-dependent manner. Moreover, LRV exacerbates disease in C57BL/6 mice but not in , and 129 mice, a mouse strain that is naturally mutant for caspase-11. These results demonstrate that LRV interferes with caspase-11 activation by , expanding our understanding about the mechanisms by which LRV promotes disease exacerbation.
该属细胞内原生动物寄生虫的新世界物种可引起黏膜皮肤利什曼病。在（.）中存在内共生利什曼原虫RNA病毒（LRV）会促进疾病恶化和黏膜皮肤疾病的发展。此前有报道称LRV会阻断NLRP3炎性小体，但其他机制仍不清楚。在这里，我们研究了LRV是否通过半胱天冬酶-11干扰炎性小体，半胱天冬酶-11可诱导非经典NLRP3激活，并且据报道可被（.）激活。通过使用巨噬细胞和小鼠，我们发现LRV以TLR3和自噬相关蛋白5（ATG5）依赖的方式抑制（.）诱导的半胱天冬酶-11激活和白细胞介素-1β释放。此外，LRV会使C57BL/6小鼠的疾病恶化，但不会使129小鼠（一种半胱天冬酶-11天然突变的小鼠品系）的疾病恶化。这些结果表明LRV通过（.）干扰半胱天冬酶-11激活，扩展了我们对LRV促进疾病恶化机制的理解。
