Compartment-Specific Remodeling of Splenic Micro-Architecture during Experimental Visceral Leishmaniasis

Abstract

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.