Background The 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. Methods The 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. Results Our 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. Conclusions In 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.

Interleukin-25 (IL-25) plays a major role in resistance against intestinal helminth infections as initiator of protective Th2 responses. However, recent studies have challenged the contribution of this cytokine in both the polarization of the response towards a Th2 phenotype and the parasite rejection. We have used the experimental model Echinostoma caproni-ICR mice to investigate the participation of this cytokine in resistance to intestinal helminths. ICR mice are characterized by their inability to respond with IL-25 production in primary infections with E. caproni, causing susceptibility associated with a Th1 response. However, mice are refractory to infection in presence of IL-25 in relation to a type 2 phenotype. Herein, we show that dynamics of resident microbiota appears to be crucial in IL-25 production. Moreover, IL-25 seems to play a pivotal role in the polarization to Th2 in primary responses, but also appears to participate in the generation of memory mechanisms making unnecessary the participation of IL-25 in memory responses for the development of Th2 milieu. However, resistance to E. caproni infection does not depend on the generation of a Th2 phenotype, but exclusively depends on the presence of IL-25, operating autonomously from the type 2 response in the generation of resistance.

Background: Interleukin-25 (IL-25) is recognized as the most relevant initiator of protective Th2 responses in intestinal helminth infections. It is well known that IL-25 induces resistance against several species of intestinal helminths, including the trematode Echinostoma caproni. Echinostoma caproni has been extensively used as an experimental model to study the factors determining the resistance to intestinal infections. Herein, we assessed the role of IL-25 in the generation of resistance in mice to E. caproni infections. Methods: To this purpose, we analyze the fatros that determine the production of IL-25 in mice experimentally infected with E. caproni and its consequences in the polarization of the immune response and the resistance to infection.Results: We have determined that the role of IL-25 in the polarization of the immune response differs between the primary and secondary response. IL-25 is required for the development of a Th2 phenotype in primary E. caproni infections but could also promote the differentiation to Th2 memory cell subsets that enhances type 2 responses in memory responses. However, development of Th2 responses does not induce resistance to infection. Th2 phenotype does not elicit resistance and IL-25 is responsible for the resistance regardless of the type 2 cytokine activity and STAT6 activation. Alternative activation of macrophages induced by IL-25 could be implicated in the resistance to infection. Conclusions: In contrast to primary infection, secondary infection elicits a type 2 response, even in the absence of IL-25 expression. Despite the development of a type 2 response, mice are susceptible to secondary infection in relation to the lack of IL-25. Resistance to infection is due to IL-25, which acts autonomously from Th2 response in the parasite clearance.

Background: Interleukin-25 (IL-25) is recognized as the most relevant initiator of protective Th2 responses in intestinal helminth infections. It is well known that IL-25 induces resistance against several species of intestinal helminths, including the trematode Echinostoma caproni. Echinostoma caproni has been extensively used as an experimental model to study the factors determining the resistance to intestinal infections. Herein, we assessed the role of IL-25 in the generation of resistance in mice to E. caproni infections. Methods: To this purpose, we analyze the fatros that determine the production of IL-25 in mice experimentally infected with E. caproni and its consequences in the polarization of the immune response and the resistance to infection.Results: We have determined that the role of IL-25 in the polarization of the immune response differs between the primary and secondary response. IL-25 is required for the development of a Th2 phenotype in primary E. caproni infections but could also promote the differentiation to Th2 memory cell subsets that enhances type 2 responses in memory responses. However, development of Th2 responses does not induce resistance to infection. Th2 phenotype does not elicit resistance and IL-25 is responsible for the resistance regardless of the type 2 cytokine activity and STAT6 activation. Alternative activation of macrophages induced by IL-25 could be implicated in the resistance to infection. Conclusions: In contrast to primary infection, secondary infection elicits a type 2 response, even in the absence of IL-25 expression. Despite the development of a type 2 response, mice are susceptible to secondary infection in relation to the lack of IL-25. Resistance to infection is due to IL-25, which acts autonomously from Th2 response in the parasite clearance.