TY - JOUR
T1 - 3d-hepatocyte culture applied to parasitology
T2 - immune activation of canine hepatic spheroids exposed to leishmania infantum
AU - Rodrigues, Armanda V.
AU - Alexandre-Pires, Graça
AU - Valério-Bolas, Ana
AU - Santos-Mateus, David
AU - Rafael-Fernandes, Mariana
AU - Pereira, Maria A.
AU - Ligeiro, Dário
AU - Nunes, Telmo
AU - Alves-Azevedo, Raquel
AU - Santos, Marcos
AU - Fonseca, Isabel Pereira da
AU - Santos-Gomes, Gabriela
PY - 2020/12/18
Y1 - 2020/12/18
N2 - 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.
AB - 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.
KW - 3D cell culture
KW - Hepatocytes
KW - Immune response
KW - Leishmania infantum
KW - Meglumine antimoniate
UR - http://www.scopus.com/inward/record.url?scp=85097939477&partnerID=8YFLogxK
UR - https://www.mdpi.com/2227-9059/8/12/628
U2 - 10.3390/biomedicines8120628
DO - 10.3390/biomedicines8120628
M3 - Article
C2 - 33352885
AN - SCOPUS:85097939477
SN - 2227-9059
VL - 8
SP - 628
EP - 649
JO - Biomedicines
JF - Biomedicines
IS - 12
M1 - 628
ER -