Characteristics of IL‐17 induction by Schistosoma japonicum infection in C57BL/6 mouse liver

Abstract

SummarySchistosomiasis japonica is a severe tropical disease caused by the parasitic worm Schistosoma japonicum. Among the most serious pathological effects of S. japonicum infection are hepatic lesions (cirrhosis and fibrosis) and portal hypertension. Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the pathogenesis of many inflammatory and infectious conditions, including schistosomiasis. We infected C57BL/6 mice with S. japonicum and isolated lymphocytes from the liver to identify cell subsets with high IL-17 expression and release using flow cytometry and ELISA. Expression and release of IL-17 was significantly higher in hepatic lymphocytes from infected mice compared with control mice in response to both non-specific stimulation with anti-CD3 monoclonal antibody plus/anti-CD28 monoclonal antibody and PMA plus ionomycin. We then compared IL-17 expression in three hepatic T-cell subsets, T helper, natural killer T and cdT cells, to determine the major source of IL-17 during infection. Interleukin-17 was induced in all three subsets by PMA + ionomycin, but cdT lymphocytes exhibited the largest increase in expression. We then established a mouse model to further investigate the role of IL-17 in granulomatous and fibrosing inflammation against parasite eggs. Reducing IL-17 activity using anti-IL-17A antibodies decreased infiltration of inflammatory cells and collagen deposition in the livers of infected C57BL/6 mice. The serum levels of soluble egg antigen (IL) -specific IgGs were enhanced by anti-IL-17A monoclonal antibody blockade, suggesting that IL-17 normally serves to suppress this humoral response. These findings suggest that cdT cells are the most IL-17-producing cells and that IL-17 contributes to granulomatous inflammatory and fibrosing reactions in S. japonicum-infected C57BL/6 mouse liver.

Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium

“…Our results showed that Sm-p80 vaccine formulated in GLA-SE induced mixed Th1 (IFN-γ, TNF-α, IL-2 and IL-12) and Th2-type immune responses which appeared to correlate with the cross-species protection observed in this S. japonicum model of infections which was in agreement with our previous studies on S. mansoni infection models (Karmakar et al 2014a; Karmakar et al 2014b). The downregulation of IL-17 observed in the S. japonicum /mouse studies (Trials 1 and 2) might not be entirely non-beneficial as studies have shown that blocking IL-17 cytokine production in S. japonicum -infected mice resulted in the reduction of granuloma formation and fibrosis (Chen et al 2013; Zhang et al 2012). Th1 and Th2 cytokines regulation in the vaccinated hamsters followed similar pattern as those in the S. japonicum infection models as we observed upregulation of Th1 cytokines (IFN-γ, TNF-α and IL-12) and Th2 cytokines (IL-4, IL-10 and IL-13) in vaccinated animals (Fig 7C and D).…”

Crusted scabies is associated with increased IL‐17 secretion by skin T cells

“…Th-17 cells play an important role in host defence against infection. In parasitic infection, however, IL-17 has been described in both protective (26) and pathologic contexts (27,28). For example, IL-27R-deficient mice infected with Toxoplasma gondii and Leishmania major develop severe disease that is characterized by a prominent IL-17 response (24).…”

Vγ1+γδT Cells Are Correlated With Increasing Expression of Eosinophil Cationic Protein and Metalloproteinase-7 in Chronic Rhinosinusitis With Nasal Polyps Inducing the Formation of Edema

“…These cells primarily colonize in the mucosa and skin where they play an important role in immune regulation 4. γδT cells have been suggested to mediate inflammatory cell infiltration and remodeling in a murine model via interleukin (IL)-17A, which has been proven to be a crucial regulator of cardiac fibrosis 5678. However, the links between γδT cells, inflammation and tissue remodeling in CRS appear to be unknown.…”