The potential roles of interleukin-25 in infectious diseases

Abstract

Interleukin-25 (IL-25), also known as IL-17E, is a recently identified cytokine of the IL-17 family. Numerous studies illustrated that the expression of IL-25 is regulated by multiple pathogens, including parasitic, viral, and bacterial infections. IL-25 has a dual function in infectious diseases. On the one hand, IL-25 activates type 2 immunity via the relevant cytokines, including IL-4, IL-5, and IL-13, which are associated with the development of pathogenic infection-related allergic diseases. On the other hand, IL-25 involves in the recruitment of group 2 innate lymphoid cells (ILC2) to enhanced T helper 2 (Th2) cell differentiation, which are important to the clearance of pathogens. However, the precise roles of IL-25 in infectious diseases remain largely unknown. Thus, the current review will shed light on the pivotal roles of IL-25 in infectious diseases.

Keywords: IL-17 family; IL-25; Th2; infectious diseases; inflammation.

Figure 1

The roles of IL-25 in parasitic infection. The up-regulation of IL-25 was induced by the infection of parasites, including helminths and arthropod parasites. In contrast, IL-25 was downregulated by protozoan infections. Whatever, parasites-induced IL-25 or rIL-25 promotes the proliferation of tuft cells. Subsequently, the cytokines of IL-4, IL-5, and IL-13 are induced by IL-25/ILC2/Th2 axis to clean the parasite. Lastly, the expression of IL-4, IL-5, and IL-13 are associated with the development of asthma, allergic rhinitis, and atopic dermatitis.

Figure 2

The roles of IL-25 in viral infection. IL-25 is up-regulated following the infection of RSV ①, HCV ②, and HSV-1 ③. Subsequently, IL-25 goes through the downstream signaling cascades by mediating the complex of receptors, consisting of IL-17RA and IL-17RB. IL-25 also induces the expression of IL-4/IL-5/IL-13, which are associated with the development of asthma. Furthermore, IL-25 overexpression was related to elevated AST and ALT involving chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. In addition, the up-regulation of IL-25 suppresses the cytokines of IFN-γ, IL-1β, IL-6, and TNF-α. However, direct evidence that IL-25 causes pathological damage is lacking.

Figure 3

The roles of IL-25 in bacterial infection. LPS is the bacteria’s component, an inducer of IL-25 expression in epithelial cells. Furthermore, the axis of IL-25/ILC2/IL-5 mediates the production of IgM, and IgM exhibits a protective effect against bacterial infection. In contrast, Ft infection suppresses the expression of IL-25, which further results in pseudomembranous colitis (PMC). The administration of rIL-25 reduces the inflammatory storm caused by the infection of Ft.