Abstract
The expression of T regulatory cells (Foxp3), regulatory (interleukin [IL]-10 and transforming growth factor beta [TGF-β]) and proinflammatory (tumor necrosis factor alpha [TNF-α] and interleukin [IL]-1β) cytokines was quantified using real time polymerase chain reaction (qRT-PCR) in the liver of sheep during early stages of infection with Fasciola hepatica (1, 3, 9, and 18 days post-infection [dpi]). Portal fibrosis was also evaluated by Masson’s trichrome stain as well as the number of Foxp3+ cells by immunohistochemistry. Animals were divided into three groups: (a) group 1 was immunized with recombinant cathepsin L1 from F. hepatica (FhCL1) in Montanide adjuvant and infected; (b) group 2 was uniquely infected with F. hepatica; and (c) group 3 was the control group, unimmunized and uninfected. An overexpression of regulatory cytokines of groups 1 and 2 was found in all time points tested in comparison with group 3, particularly at 18 dpi. A significant increase of the number of Foxp3+ lymphocytes in groups 1 and 2 was found at 9 and 18 dpi relative to group 3. A progressive increase in portal fibrosis was found in groups 1 and 2 in comparison with group 3. In this regard, group 1 showed smaller areas of fibrosis than group 2. There was a significant positive correlation between Foxp3 and IL-10 expression (by immunohistochemistry and qRT-PCR) just as between portal fibrosis and TGF-β gene expression. The expression of proinflammatory cytokines increased gradually during the experience. These findings suggest the induction of a regulatory phenotype by the parasite that would allow its survival at early stages of the disease when it is more vulnerable.
Highlights
Fasciolosis, caused by Fasciola hepatica, produces high economic losses to the agricultural sector [1]
The results of the present study revealed a significant increase in T regulatory cells (forkhead box P3 transcription factor (Foxp3)+) detected by immunohistochemistry and gene expression in liver of both infected control and immunized sheep compared to the uninfected control group at 9 and 18 dpi
These results are in agreement with the significant increase of this cell type described in goats and sheep experimentally infected with F. hepatica at 9 dpi [12] and with the increase of T regulatory cells (Foxp3+) in the abomasum of sheep infected with Teladorsagia circumincta [11] and suggests that both parasites induce expansion of Foxp3+ T cells to modulate the host response facilitating their survival in host tissues
Summary
Fasciolosis, caused by Fasciola hepatica, produces high economic losses to the agricultural sector [1] This parasite infects a wide range of domestic animals including cattle, sheep, and goats, and the disease has been recognized as an important zoonosis in Africa, Asia, Europa, America, and Oceania [2, 3]. It has been reported that F. hepatica is able to downregulate the Th1 immune response and upregulate the Th2 response at early stages of infection in sheep [13] and mice [14] as well as in chronic stages in cattle [15]. This imbalance towards a Th2 immune profile is mediated through regulatory cytokines and cells that modulate and/or suppress inflammatory responses. F. hepatica develops other mechanisms to evade the host’s immune response in early stages in sheep where larvae are able to induce apoptosis of peritoneal leukocytes, allowing the migration of larvae through the peritoneum [19]
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