The balance between IL-12/IL4 in renal tissue switches the inflammatory response arm and shows relationship with the clinical signs in Leishmania-infected dogs

• Published in: Veterinary immunology and immunopathology Vol. 234; p. 110196
• Main Authors: Verçosa, Bárbara L.A., Muniz-Junqueira, Maria Imaculada, Menezes-Souza, Daniel, Fujiwara, Ricardo Toshio, Melo, Maria N., Vasconcelos, Anilton C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2021
• Subjects: Canine leishmaniosis; chi-square distribution; Cytokines; dogs; eosin; gene expression; immunopathology; Inflammation; interferon-gamma; interleukin-10; interleukin-12; interleukin-4; Kidney; kidneys; Leishmania; leishmaniasis; morphometry; pathogenesis; tumor necrosis factor-alpha; Inflammation; Cytokines; Canine leishmaniosis; Kidney
• ISSN: 0165-2427; 1873-2534; 1873-2534
• DOI: 10.1016/j.vetimm.2021.110196

[Display omitted] •Renal inflammation in CanL is not associated with tissue infection by Leishmania.•Kidneys showed more inflammatory cells in the dogs that showed greater clinical signs.•The balance between IL-4 and IL-12 was critically determinant of the clinical signs (r = 0.70, Spearman test, p = 0.007).•IL-4 was enhanced in symptomatic dogs.•IL-12 was more enhanced than IL-4 possibly switching the response inflammatory arm. The pathogenesis of Canine leishmaniosis (CanL) is associated with altered cytokine expression and parasitic tissue shows a lot of inflammation. The aim of this study was to assess the renal inflammation and cytokine expression in eight symptomatic and eight asymptomatic Leishmania- infected dogs, and seven uninfected control dogs. Kidney fragments were stained with hematoxylin and eosin for morphometric evaluation. mRNA expression levels of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, IL-4, IL-10, and IL-12 were assessed in the kidney fragments using quantitative real time-polymerase chain reaction. Inflammation, quantified by the average area of the infiltrated immune cells, was greater in symptomatic dogs than in those asymptomatic, whereas asymptomatic dogs exhibited higher inflammation than the control dogs (p > 0.05, Tukey’s test). Expression levels of IFN-γ, TNF-α, IL-4, IL-10, and IL-12 were upregulated in symptomatic dogs and downregulated in asymptomatic dogs compared with those of the uninfected group. Furthermore, IL-4 showed higher expression in symptomatic dogs than in asymptomatic ones (p < 0.05, Mann-Whitney test), which was directly associated with clinical manifestations (p < 0.05, Chi-square test). However, IL-12 was predominantly expressed in symptomatic dogs, shifting the balance from IL-12/IL-4 to IL-12, which elicits a change in the inflammatory response. Leishmania was not found in the renal tissues in any one of the studied groups. Our data suggests that the balance between IL-12 and IL-4 plays an important role in the regulation of inflammation in renal tissue and clinical presentations in CanL.