Abstract
BackgroundThe liver plays a central role in the development of canine visceral leishmaniasis. Studies of natural infection in animals and humans indicate a direct relationship between resolution of infection and the formation and maturation of granulomas in the liver. However, in contrast to other reports in the literature, the present study found no differences in the characteristics of hepatic granulomas that could be related to resistance or susceptibility to Leishmania. Here, we describe the hepatic alterations observed in dogs with differing clinical manifestations of visceral leishmaniasis in an endemic area in the state of Bahia, Brazil.MethodsWe examined 148 animals in an endemic area. The animals were clinically examined, and the infection was determined by ELISA, spleen aspirate culture and quantitative PCR. The animals were grouped into asymptomatic or symptomatic based on the number of signs of LV. The histological liver evaluation was performed in a blinded way.ResultsOur results indicated no association between the characteristics of granulomas and clinical presentation. We found an association between the intensity of this inflammatory response and parasite load in the animals’ spleens. It is important to note that while hepatic alterations, such as portal and perivascular inflammation and the presence of larger amounts of granulomas, were linked with higher parasite loads, we found the inverse to be true with respect to intrasinusoidal lymphocytosis, the formation of intrasinusoidal inflammatory cell aggregates and Kupffer cell hypertrophy.ConclusionsOur findings suggest that the presence of mononuclear inflammatory cells inside the sinusoids is more important than that of organized granulomas in terms of the containment of parasitism by the host. We suggest that the presence of granulomas indicates the failure of a first line of defense mechanism in the control of parasite infection, which could be related to the presence of inflammatory cells and Kupffer cell hypertrophy inside the sinusoids. We further demonstrated that dogs with active Leishmania spp. infection present a higher frequency of inflammatory changes in the liver. In addition to being correlated with the severity of clinical manifestation, these hepatic alterations were also associated with changes in hematological and biochemical parameters.
Highlights
The liver plays a central role in the development of canine visceral leishmaniasis
Inflammatory infiltrate consisting of macrophages, lymphocytes and plasma cells was found to be prominent around the centrilobular vein (Fig. 1d)
Intralobular granulomas were dispersed throughout the hepatic parenchyma (Fig. 1e, f ), varying from loosely organized structures composed of Kupffer cells, which were occasionally parasitized, lymphocytes and plasma cells, to well-organized concentric Kupffer cells surrounded by lymphocytes and rare plasma cells (Fig. 1e, f )
Summary
The liver plays a central role in the development of canine visceral leishmaniasis. Studies of natural infection in animals and humans indicate a direct relationship between resolution of infection and the formation and maturation of granulomas in the liver. In the course of an outbreak in Italy, Pampiglione et al [12, 13] biopsied the livers of five asymptomatic patients with positive DTH for Leishmania antigens and observed intralobular granulomas consisting of accumulations of epithelioid macrophages, histiocytes, lymphocytes, plasma cells and rare eosinophils. This same granulomatous inflammatory pattern in the liver has been correlated with resistance in non-susceptible mice [14, 15]
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