Bone marrow fat and expression of bone marrow hematopoiesis modulating genes in dogs with visceral leishmaniasis

Abstract

Progenitor cells of the hematopoietic system, such as myeloid progenitors and lymphoid progenitors, increase immune cell production to restore and maintain homeostasis during chronic infection. Bone marrow adipose tissue affects the proportion and differentiation of bone marrow stem cells by production of adiponectin, leptin, prostaglandins, IL-6 and other adipocyte-related factors.The bone marrow is usually heavily parasitized in infected dogs. Initially, erythropoiesis and granulopoiesis are not normal, but functional imbalances occur in these processes, during the more advanced phases of the infection, and lead to a decrease in cell production, with repercussions on the hematological condition. This change occurs through histiocytic hyperplasia, erythrocytic hypoplasia and, as the disease progresses, to aplasia. Although the bone marrow is significantly affected in canine visceral leishmaniasis, studies on the different pathological aspects that affect the hematopoietic and adipose tissue of the bone marrow are less frequent than studies carried out on lymph nodes and spleen.Our current objective is to verify, in dogs naturally infected with L. infantum, whether the amount of bone marrow fat influences the production of factors that stimulate hematopoiesis. The pathogenesis and worsening of clinical signs observed in dogs infected with L. infantum are related to a dysfunction in the production and separation of cells derived from the bone marrow related to the immune and inflammatory response. Changes in cellular composition and bone marrow fat are already described in dogs with visceral leishmaniasis. As reported in other natural diseases and/or experimental models, changes in the bone marrow microenvironment can interfere with the hematopoiesis process. Therefore, our goal is to study the relative expression of RNAs of hematopoiesis-modulating substances that are produced by stromal cells, including bone marrow adipocytes, by comparing the pattern of gene expression between healthy dogs and dogs infected with L. infantum. The amount of adipose tissue present in the dogs' bone marrow will also be considered.