The application of innovative three-dimensional (3D) spheroids cell culture strategy to Parasitology offers the opportunity to closely explore host–parasite interactions. Here we present a first report on the application of 3D hepatic spheroids to unravel the immune response of canine hepatocytes exposed to Leishmania infantum. The liver, usually considered a major metabolic organ, also performs several important immunological functions and constitutes a target organ for L. infantum infection, the etiological agent of canine leishmaniasis (CanL), and a parasitic disease of major veterinary and public health concern. 3D hepatic spheroids were able to sense and immunologically react to L. infantum parasites, generating an innate immune response by increasing nitric oxide (NO) production and enhancing toll-like receptor (TLR) 2 and interleukin-10 gene expression. The immune response orchestrated by canine hepatocytes also lead to the impairment of several cytochrome P450 (CYP450) with possible implications for liver natural xenobiotic metabolization capacity. The application of meglumine antimoniate (MgA) increased the inflammatory response of 3D hepatic spheroids by inducing the expression of Nucleotide oligomerization domain (NOD) -like receptors 1 and NOD2 and TLR2, TLR4, and TLR9 and enhancing gene expression of tumour necrosis factor α. It is therefore suggested that hepatocytes are key effector cells and can activate and orchestrate the immune response to L. infantum parasites.

• 3D cell culture
• Leishmania infantum
• hepatocytes
• immune response
• meglumine antimoniate

Both parasitology and stem cell research are important disciplines in their own right. Parasites are a real threat to human health causing a broad spectrum of diseases and significant annual rates morbidity and mortality globally. Stem cell research, on the other hand, focuses on the potential for regenerative medicine for a range of diseases including cancer and regenerative therapies. Though these two topics might appear distant, there are some “unexpected encounters”. In this review, we summarise the various links between parasites and stem cells. First, we discuss how parasites’ own stem cells represent interesting models of regeneration that can be translated to human stem cell regeneration. Second, we explore the interactions between parasites and host stem cells during the course of infection. Third, we investigate from a clinical perspective, how stem cell regeneration can be exploited to help circumvent the damage induced by parasitic infection and its potential to serve as treatment options for parasitic diseases in the future. Finally, we discuss the importance of screening for pathogens during organ transplantation by presenting some clinical cases of parasitic infection following stem cell therapy.

• Stem cells
• Parasites
• Transplantation
• Therapeutic
• Host pathogen interactions

• Hepatocytes
• Leishmania infantum
• innate immunity
• meglumine antimoniate

• Animals
• Disease Models, Animal
• Humans
• Leishmania infantum/pathogenicity
• Leishmaniasis, Visceral/metabolism
• Leishmaniasis, Visceral/parasitology
• Leishmaniasis, Visceral/pathology
• Male
• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cells/parasitology
• Mesenchymal Stem Cells/pathology
• Mice
• Mice, Inbred C57BL
• Receptors, Nerve Growth Factor/metabolism
• Stem Cell Niche

• CAPES

• Antiprotozoal Agents/therapeutic use
• Biopsy
• Humans
• Leishmaniasis, Visceral/diagnosis
• Leishmaniasis, Visceral/drug therapy
• Leishmaniasis, Visceral/immunology
• Liver/parasitology
• Liver/pathology
• Liver Diseases, Parasitic/diagnosis
• Liver Diseases, Parasitic/drug therapy
• Liver Diseases, Parasitic/immunology