Abstract
BackgroundThe cytokine interleukin-25 (IL-25) is recognized as the most relevant initiator of protective T helper 2 (Th2) responses in intestinal helminth infections. This cytokine induces resistance against several species of intestinal helminths, including the trematode Echinostoma caproni. E. caproni has been extensively used as an experimental model to study the factors determining resistance to intestinal infections. In the study reported here, we assessed the role of IL-25 in the generation of resistance in mice infected with E. caproni.MethodsThe factors that determine the production of IL-25 in mice experimentally infected with E. caproni were determined, as were the consequences of IL-25 production in terms of polarization of the immune response and resistance to infection.ResultsOur results show that the role of IL-25 in the polarization of the immune response differs between the primary and secondary immune responses. IL-25 is required for the development of a Th2 phenotype in primary E. caproni infections, but it can also promote the differentiation to Th2 memory cell subsets that enhance type-2 immunity in memory responses. However, the development of Th2 responses does not induce resistance to infection. The Th2 phenotype does not elicit resistance, and IL-25 is responsible for the resistance regardless of its type-2 cytokine activity and activation of signal transducer and activator of transcription (STAT6). Alternative activation of macrophages induced by IL-25 can be implicated in the resistance to infection.ConclusionsIn contrast to primary infection, secondary infection elicits a type-2 immune response even in the absence of IL-25 expression. Despite the development of a type-2 response, mice are susceptible to secondary infection associated with the lack of IL-25. Resistance to infection is due to the production of IL-25, which acts autonomously from Th2 response in terms of parasite clearance.Graphical
Highlights
The cytokine interleukin-25 (IL-25) is recognized as the most relevant initiator of protective T helper 2 (Th2) responses in intestinal helminth infections
It is not well defined if the participation of IL-25 is limited to its ability to promote Th2 responses or if it is directly involved in the activation of effector mechanisms responsible for resistance
No significant differences between groups were detected in the remaining cytokines nor in the expression of markers of macrophage activation
Summary
The cytokine interleukin-25 (IL-25) is recognized as the most relevant initiator of protective T helper 2 (Th2) responses in intestinal helminth infections. While recent studies have uncovered the origin and the mechanisms of action of IL-25 [13,14,15], several doubts remain concerning the role of IL-25 in the generation of protective Th2 responses to intestinal helminth infections [8, 16, 17]. It is not well defined if the participation of IL-25 is limited to its ability to promote Th2 responses or if it is directly involved in the activation of effector mechanisms responsible for resistance. Several recent studies have questioned the role of IL-25 on the generation of adaptive type-2 immune responses or on the differentiation of Th2 cells or their development to effector or memory Th2-cell subsets [8, 16]
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