Laboratory of Molecular Immunology, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Laboratory of Applied Genetics, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
PLoS Negl Trop Dis. 2020 Jan 21;14(1):e0008020. doi: 10.1371/journal.pntd.0008020. eCollection 2020 Jan.
Myeloid-related protein 14 (MRP14) belongs to the S100 calcium-binding protein family and is expressed in neutrophils and inflammatory macrophages. Increase in the number of MRP14+ cells or serum level of MRP14 is associated with various diseases such as autoimmune diseases and infectious diseases, suggesting the involvement of the molecule in pathogenesis of those diseases. In this study, to examine the pathological involvement of MRP14 during cutaneous and visceral leishmaniasis, wild-type (WT) and MRP14 knockout (MRP14KO) mice were infected with Leishmania major and L. donovani. Increase in the number of MRP14+ cells at the infection sites in wild-type mice was commonly found in the skin during L. major infection as well as the spleen and liver during L. donovani infection. In contrast, the influence of MRP14 to the pathology seemed different between the two infections. MRP14 depletion exacerbated the lesion development and ulcer formation in L. major infection. On the other hand, the depletion improved anemia and splenomegaly but not hepatomegaly at 24 weeks of L. donovani infection. These results suggest that, distinct from its protective role in CL, MRP14 is involved in exacerbation of some symptoms during VL.
髓系相关蛋白 14（MRP14）属于 S100 钙结合蛋白家族，在中性粒细胞和炎症巨噬细胞中表达。MRP14+细胞数量的增加或 MRP14 的血清水平与各种疾病相关，如自身免疫性疾病和传染病，表明该分子参与了这些疾病的发病机制。在这项研究中，为了研究 MRP14 在皮肤和内脏利什曼病中的病理作用，野生型（WT）和 MRP14 敲除（MRP14KO）小鼠感染了大疱性表皮松解症和利什曼原虫。在 WT 小鼠的感染部位，MRP14+细胞数量的增加在大疱性表皮松解症感染的皮肤以及利什曼原虫感染的脾脏和肝脏中普遍存在。相比之下，MRP14 对两种感染的病理影响似乎不同。MRP14 耗竭加剧了大疱性表皮松解症感染中的病变发展和溃疡形成。另一方面，在利什曼原虫感染 24 周时，耗竭可改善贫血和脾肿大，但不能改善肝肿大。这些结果表明，与 CL 中的保护作用不同，MRP14 参与了 VL 中某些症状的加重。
