Histological Disorganization of Spleen Compartments and Severe Visceral Leishmaniasis

Abstract

The spleen is a secondary lymphoid organ responsible for immune surveillance against blood-circulating pathogens. Absence of the spleen is associated with increased susceptibility to systemic spread and fatal infection by different pathogens. Severe forms of visceral leishmaniasis are associated with disorganization of spleen compartments where cell interactions essential for splenic immunological function take place. White pulp atrophies, secondary lymphoid follicles and marginal zones vanish, and the boundaries separating white and red pulp blur. Leukocyte populations are reduced or disappear or are replaced by plasma cells. In this paper, we review the published data on spleen disorganization in severe forms of visceral leishmaniasis and propose a histological classification to help the exchange of information among research groups.

Keywords: Leishmania infantum; spleen disorganization; spleen pathology; visceral leishmaniasis; white pulp disruption.

Figure 1

Spleen compartments in human (A,D), dog (B,E), and hamster (C,F) spleen. Spleen in all three species presents white and red pulp (RP). White pulp presents periarteriolar lymphocyte sheath (P) and lymphoid follicles with a germinal centers (GC) and mantle region (M) surrounded by a loosely distributed marginal zone (MZ). These spleen compartments are more clearly seen in human and dogs than in rodent spleens. Hematoxilyn-eosin staining, scale bar in (A–C) = 100 μm; in (D–F) = 50 μm.

Figure 2

Class of spleen disorganization according to disruption of white pulp structures. Hematoxilyn-eosin staining, scale bar in the top row = 400 μm; in the bottom row = 200 μm.

Figure 3

Proposed sequence of events in spleen disorganization: (A) Normal spleen with well-defined white and red pulp compartments: Red pulp (RP) with a mixed leukocyte population with lymphocytes, macrophages and some plasma cells. Marginal zone (MZ) containing lymphocyte and macrophages. Lymphoid follicle (LF) containing lymphocytes and follicular dendritic cells. Periarteriolar lymphocyte sheath (PALS) containing mostly predominantly lymphocytes. The integrity of spleen compartments is dependent on chemokines such as CCL19 and CCL21 (PALS), CXCL13 (LF). (B) After Leishmania infection amastigote-containing macrophages are observed in the different spleen compartments. (C) Antigen stimulation and polyclonal B cell activation leads to white pulp hyperplasia and plasma cell accumulation in the RP. (D) T lymphocyte and follicular dendritic cell apoptosis leads to a reduction of CXCL13 chemokine expression and white pulp disruption. Inflammatory changes of red pulp enhance B-cell activating factor (BAFF), A proliferation-inducing ligand (APRIL) and CXCL-12 chemokine expression, favoring plasma cells homing and survival.