MCP-1/IL-12 ratio expressions correlated with adventitial collagen depositions in renal vessels and IL-4/IFN-γ expression correlated with interstitial collagen depositions in the kidneys of dogs with canine leishmaniasis

Abstract

Collagen deposition is a common event in chronic inflammation, and canine Leishmaniosis (CanL) is generally associated with a long and chronic evolution. Considering that the kidney shows fibrinogenic changes during CanL, and the balance of cytokines/chemokines regulates the profibrinogenic and antifibrinogenic immune responses differently, it can be hypothesized that the balance of cytokines/chemokines can be differentially expressed in the renal tissue in order to determine the expression of collagen depositions in the kidneys. This study aimed to measure collagen deposition and to evaluate cytokine/chemokine expressions in the kidney by means of qRT-PCR in sixteen Leishmania-infected dogs and six uninfected controls. Kidney fragments were stained with hematoxylin & eosin (H&E), Masson’s Trichrome, Picrosirius Red, and Gomori’s reticulin. Intertubular and adventitial collagen depositions were evaluated by the morphometric approach. Cytokine RNA expressions were measured by means of qRT-PCR to identify molecules involved in chronic collagen depositions in kidneys with CanL. Collagen depositions were related to the presence of clinical signs, and more intense intertubular collagen depositions occurred in infected dogs. Adventitial collagen deposition, as morphometrically measured by the average area of the collagen, was more intense in clinically affected dogs than in subclinically infected dogs. TNF-α/TGF-β, MCP1/IL-12, CCL5/IL-12, IL-4/IFN-γ, and IL-12/TGF-β expressions were associated with clinical manifestations in dogs with CanL. The IL-4/IFN-α ratio was more commonly expressed and upregulated in clinically affected dogs, and downregulated in subclinically infected dogs. Furthermore, MCP-1/IL-12 and CCL5/IL-12 were more commonly expressed in subclinically infected dogs. Strong positive correlations were detected between morphometric values of interstitial collagen depositions and MCP-1/IL-12, IL-12, and IL-4 mRNA expression levels in the renal tissues. Adventitial collagen deposition was correlated with TGF-β, IL-4/IFN-γ, and TNF-α/TGF-β. In conclusion, our results showed the association of MCP-1/IL-12 and CCL5/IL-12 ratios with an absence of clinical signs, as well as an IL-4/IFN-α ratio with adventitial and intertubular collagen depositions in dogs with visceral leishmaniosis.