Abstract
The spleen is one of the main affected organs in canine visceral leishmaniasis (CVL). Disorganization of the splenic white pulp (SWP) has been associated with immunosuppression and disease progression. This study aims to assess structural and cellular changes in the splenic extracellular matrix of dogs with CVL, correlating these changes with the parasite load and clinical signs. Splenic fragments were collected from 41 naturally infected animals for parasite load quantification by quantitative PCR, histopathological analysis and immunohistochemistry for CD3+, CD4+, and CD8+ T cells; CD21+ B cells; Ki-67+, IFN-γ+, and IL-10+ cells; and the MMP-9 and ADAM-10 enzymes. Laminin, collagen and fibronectin deposition were also evaluated. The animals were grouped according to the level of SWP organization. SWP disorganization was accompanied by a reduction in the quantity of lymphoid follicles/mm2 (p > 0.0001). Animals with moderate to intense SWP disorganization showed more clinical signs (p = 0.021), higher laminin (p = 0.045) and collagen deposition (p = 0.036), higher MMP-9 expression (p = 0.035) and lower numbers of CD4+ T cells (p = 0.027) in the spleen than the animals with organized SWP. These data suggest that splenic structure and function are drastically altered and compromised during CVL.
Highlights
In Brazil, visceral leishmaniasis is caused by Leishmania infantum, and the domestic dog is the main urban reservoir[1]
We found an association between extracellular matrix alterations and a failure to control the parasite load
We suggest a role for these alterations in hindering an immune response that is otherwise able to control the parasite load, thereby leading to disease progression
Summary
In Brazil, visceral leishmaniasis is caused by Leishmania infantum, and the domestic dog is the main urban reservoir[1]. Laminin, fibronectin and collagen, are important proteins that constitute the basal and interstitial membranes of this organ and are fundamental to the structuring and maintenance of the white pulp, contributing to the upkeep of cellular compartmentalization. These proteins contribute to the cellular communication and transport of cytokines and chemokines through structures known as sinusoids and conduits, which comprise type IV collagen, laminin and reticular fibroblasts[8,9,10]. Differences in the localizations of extracellular matrix (ECM) molecules in the spleen suggest that the ECM plays a role in the compartmentalization of immune cells to their respective niches, and clearly, future analyses of ECM animal models require the consideration of possible immunological defects[10]
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