The Potential Role of Th9 Cell Related Cytokine and Transcription Factors in Patients with Hepatic Alveolar Echinococcosis

Abstract

Human alveolar echinococcosis (AE) is a lethal parasitic infectious disease which may lead to liver failure if left untreated. It is caused by the larval stage of the fox tapeworm Echinococcus multilocularis and usually develops a substantial infiltrative occupation in solid organs. During the infection, T helper subsets are known to play crucial role in crosstalk between the parasite and human host. Th9 cells, a new member of CD4+ T cell family which is characterized by its specific cytokine IL-9 and transcription factors PU.1 and IRF-4, have been known recently to have a critical role in allergic diseases, and cancers as well as the parasitic infection. To assess the potential role of Th9 cells during the infection, the mRNA levels of IL-9, PU.1, and IRF-4 both in peripheral blood mononuclear cells and in liver tissues were, respectively, detected by using real-time PCR. The plasma concentration levels of IL-9 were detected by using enzyme linked immunosorbent assay (ELISA). Th9 related cytokine IL-9 and transcription factors PU.1 and IRF-4 mRNA levels elevated both in PBMCs, and in hepatic lesion and paralesion tissues in AE patients. This may facilitate the infiltrative growth of the parasite and its persistence in human host.

Plasma IL-23 and IL-5 as surrogate markers of lesion metabolic activity in patients with hepatic alveolar echinococcosis

“…It also serves to stabilize and expand Th17 cell functions and to enhance the expression of IL-17 in granulomatous lesions 27 , 28 . The immunopathological consequences of increased IL-17 production have been shown in both human and experimental AE 10 , 11 . Besides, elevated Th17 cell response might increase angiogenesis and inflammation that provides a new environment and nutrition to the parasite while accelerating disease progression 29 .…”

“…Growing evidence supports that increased FDG uptake measured by PET in patients with progressing AE is based on the periparasitic cell infiltration and thus reflects the cross-talk between the parasite and human host’s immune cells 9 . Several studies have focused on this cross-talk and the possible role of dendritic cells, T helper (Th) cells and the cytokines they produce both in humans and experimental models 10 , 11 . They have usually separately addressed peripheral or regional immune response; in addition, comparison between progression, stability or regression of lesions, whenever studied, was assessed on clinical grounds only 12 – 14 .…”

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

“…However, it has been recently shown that IL‐9 and IL‐4 were rarely produced by the same T cell, indicating that Th9 cells form a unique Th cell subset . The critical roles of IL‐9 in a broad range of autoimmune disorders, allergic inflammation and cancers, as well as parasitic infection, has aroused interest . However, studies on the relationship between IL‐9 and schistosomiasis are scarce.…”

“…23 The critical roles of IL-9 in a broad range of autoimmune disorders, allergic inflammation and cancers, as well as parasitic infection, has aroused interest. [24][25][26][27][28][29][30] However, studies on the relationship between IL-9 and schistosomiasis are scarce. Our previous study investigated the dynamic changes of Th9/IL-9 in S. japonicum-infected mice and found that egg granulomas developed synchronously with the expression changes of IL-9 and PU.1 in liver.…”

The correlations between Th1 and Th2 cytokines in human alveolar echinococcosis

“…Tuxun et al [10] IL-10 and TGF-β levels are high in the course of AEprogression in humans. Gottstein et al [20] IL-12, IL-23, IL-17A, IL-17F, and IL-10 levels were higher in patients with hepatic AE.…”