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

TY - JOUR

T1 - Compartment-Specific Remodeling of Splenic Micro-Architecture during Experimental Visceral Leishmaniasis

AU - Yurdakul, Pinar

AU - Dalton, Jane Elise

AU - Beattie, Lynette

AU - Brown, Nlajmeeyah

AU - Erguven, Sibel

AU - Maroof, Asher

AU - Kaye, Paul M.

N1 - Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2011/7

Y1 - 2011/7

N2 - 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. (Am J Palbol 2011, 179:23-29; 1)01: 10.1016/j.ajpath.2011.03.009)

AB - 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. (Am J Palbol 2011, 179:23-29; 1)01: 10.1016/j.ajpath.2011.03.009)

KW - Animals

KW - Antibodies, Monoclonal

KW - Antigens, Ly

KW - B-Lymphocytes

KW - Blotting, Western

KW - Cells, Cultured

KW - Cricetinae

KW - Dendritic Cells

KW - Female

KW - Fibroblasts

KW - Flow Cytometry

KW - Immunoenzyme Techniques

KW - Leishmania donovani

KW - Leishmaniasis, Visceral

KW - Macrophages

KW - Mesocricetus

KW - Mice

KW - Mice, Inbred C57BL

KW - Monocytes

KW - Neovascularization, Pathologic

KW - Neutrophils

KW - Spleen

KW - Splenomegaly

UR - http://www.scopus.com/inward/record.url?scp=80052494648&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2011.03.009

DO - 10.1016/j.ajpath.2011.03.009

M3 - Article

C2 - 21703391

SN - 0002-9440

VL - 179

SP - 23

EP - 29

JO - American Journal of Pathology

JF - American Journal of Pathology

IS - 1

ER -