Abstract
Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum, which is transmitted by phlebotomine sandflies. Dogs are the main urban reservoir of this parasite and the disease presents similar characteristics in both humans and dogs. In this paper, we investigated the potential pathways involved in plasma cell replacement of normal cell populations in the spleen, with respect to disease severity in dogs from an endemic area for visceral leishmaniasis. To this end, canine spleen samples were grouped into three categories: TYPE1SC- (non-infected dogs or without active infection with organized white pulp), TYPE1SC+ (infected dogs with organized white pulp) or TYPE3SC+ (infected animals with disorganized white pulp). We analyzed the distribution of different plasma cell isotypes (IgA, IgG and IgM) in the spleen. The expression of cytokines and chemokines involved in plasma cell homing and survival were assessed by real time RT-PCR. Polyclonal B cell activation and hypergammaglobulinemia were also evaluated. The proportion of animals with moderate or intense plasmacytosis was higher in the TYPE3SC+ group than in the other groups (Fisher test, P<0.05). This was mainly due to a higher density of IgG+ plasma cells in the red pulp of this group. The albumin/globulin ratio was lower in the TYPE3SC+ animals than in the TYPE1SC- or TYPE1SC+ animals, which evidences VL-associated dysproteinemia. Interestingly, TYPE3SC+ animals showed increased expression of the BAFF and APRIL cytokines, as well as chemokine CXCL12. Aberrant expression of BAFF, APRIL and CXCL12, together with amplified extrafollicular B cell activation, lead to plasma cell homing and the extended survival of these cells in the splenic red pulp compartment. These changes in the distribution of immunocompetent cells in the spleen may contribute to the progression of VL, and impair the spleen’s ability to protect against blood borne pathogens.
Highlights
The spleen is a secondary lymphoid organ involved in the surveillance against bloodborne pathogens [1]
The present study investigated some of the factors associated with plasma cell accumulation that persists in the spleens of dogs with visceral leishmaniasis (VL) even after white pulp disorganization
The present study clearly demonstrates that, in severe canine VL, the disruption of splenic white pulp is associated with more frequent and intense plasma cell accumulation in the spleen
Summary
The spleen is a secondary lymphoid organ involved in the surveillance against bloodborne pathogens [1]. The absence of the spleen secondary to surgery or hematological diseases is associated with an increased risk of sepsis, as well as overwhelming infections by viruses, bacteria, protozoa and fungi [3,4]. The process of white pulp disorganization is associated with parasite burden, T lymphocyte apoptosis, decreased follicular dendritic cell counts and CXCL13 expression in the spleen, and severe clinical disease [14,15,16,17]. We know little regarding how plasma cell accumulation contributes to the progression of VL, the presence of white pulp disruption together with plasmacytosis evidences profound changes in lymphocyte differentiation within the spleen [12,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
