Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom.
Am J Pathol. 2011 Jul;179(1):23-9. doi: 10.1016/j.ajpath.2011.03.009. Epub 2011 Apr 30.
Progressive splenomegaly is a hallmark of visceral leishmaniasis in humans, canids, and rodents. In experimental murine visceral leishmaniasis, splenomegaly is accompanied by pronounced changes in microarchitecture, including expansion of the red pulp vascular system, neovascularization of the white pulp, and remodeling of the stromal cell populations that define the B-cell and T-cell compartments. Here, we show that Ly6C/G(+) (Gr-1(+)) cells, including neutrophils and inflammatory monocytes, accumulate in the splenic red pulp during infection. Cell depletion using monoclonal antibody against either Ly6C/G(+) (Gr-1; RB6) or Ly6G(+) (1A8) cells increased parasite burden. In contrast, depletion of Ly6C/G(+) cells, but not Ly6G(+) cells, halted the progressive remodeling of Meca-32(+) and CD31(+) red pulp vasculature. Strikingly, neither treatment affected white pulp neovascularization or the remodeling of the fibroblastic reticular cell and follicular dendritic cell networks. These findings demonstrate a previously unrecognized compartment-dependent selectivity to the process of splenic vascular remodeling during experimental murine visceral leishmaniasis, attributable to Ly6C(+) inflammatory monocytes.
进行性脾肿大是人类、犬科动物和啮齿动物内脏利什曼病的一个标志。在实验性内脏利什曼病的小鼠模型中，脾肿大伴随着微结构的显著变化，包括红髓血管系统的扩张、白髓的新生血管形成以及定义 B 细胞和 T 细胞区室的基质细胞群体的重塑。在这里，我们表明 Ly6C/G(+)（Gr-1(+)）细胞，包括中性粒细胞和炎症性单核细胞，在感染期间积聚在脾脏的红髓中。使用针对 Ly6C/G(+)（Gr-1；RB6）或 Ly6G(+)（1A8）细胞的单克隆抗体进行细胞耗竭会增加寄生虫负担。相比之下，耗竭 Ly6C/G(+)细胞而不是 Ly6G(+)细胞会阻止 Meca-32(+)和 CD31(+)红髓脉管的进行性重塑。引人注目的是，两种治疗均未影响白髓的新生血管形成或成纤维网状细胞和滤泡树突状细胞网络的重塑。这些发现表明，在实验性内脏利什曼病的小鼠模型中，脾脏血管重塑过程存在以前未被认识到的与细胞区室相关的选择性，这归因于 Ly6C(+)炎症性单核细胞。
