**Acknowledgements**

*Immune Response Activation and Immunomodulation*

role of IL-1β is not well understood [159].

to the development of immunopathology [178] (**Figure 5**).

Although cytokines are produced with the purpose of modulating the immune response against infections caused by microorganisms, such as bacteria, fungi, viruses, and parasites, there is evidence that these microorganisms can induce cytokine production with bad prognostic to host recovery. In this sense, overproduction

intestinal infection by helminth parasites [150, 151, 159], which is necessary in the protection against the parasite through the Th2 immune response [160]. However, several studies have associated the production of TNF-α with the development of intestinal pathology during infection by helminth parasites [155, 161, 162]. One of the effects of TNF-α is the iNOS expression and consequently the NO production [163–165]. Helminth parasite antigens are capable to induce the expression of iNOS, with the subsequent production of NO [166], which acts mainly as an effector molecule against both extracellular and intracellular parasites [167]. Studies in iNOS knockout mice infected with helminth parasites, showed a reduction in the expression of Th2 cytokines (IL-4, IL-5), a reduced humoral response (IgG and IgE), with a decrease in mastocytosis. However, no significant difference was observed in the helminth parasite expulsion, although iNOS knockout mice showed a decrease in intestinal pathology compared to wild-type animals. These results suggest that NO is not required for the helminth parasite expulsion, but its production is responsible for the intestinal pathology [155, 168]. With respect to IL-1β, it is well known that it participates in the intestinal inflammatory response in the helminth parasites infection, observing high levels during intestinal infection. However, until now, the

With respect to the Th2 type immune response, in vitro studies have shown that helminth parasite antigens are capable of dendritic cells activating, inducing the synthesis of Th2 cytokines such as IL-4, IL-5, IL-10, and IL-13 [147, 149, 153, 169]. Likewise, studies in in vivo models have shown that helminth parasites infection is a significant increase in the synthesis of IL-4, IL-5, IL-10, and IL-13 [150, 151, 159, 170] (**Figure 5**). IL-10 may suppress antigen presentation by dendritic cells and inhibition of IL-12 secretion. In addition, helminth parasite antigens increased both IL-4 and IL-10 production derived from Th2 cells with a decrease in INF-γ production, polarizing the immune response to a strong Th2 cellular immune response, protective and responsible for the helminth parasite expulsion [143]. IL-10 is a Th2 cytokine, which is necessary for a successful intestinal immune response. This is because the absence or decrease of IL-10 causes a significant delay in the helminth parasite expulsion and an increase in the parasite burden [171]. IL-4 and IL-13 induce muscle cells hypercontractility of the jejunum and intestinal mastocytosis, promoting the helminth parasite expulsion [161, 172]. In IL-4/IL-13 mice deficient, a reduction in the helminth parasite expulsion, mastocytosis, and development of intestinal pathology was observed [161, 162, 173, 174]. Therefore, these studies suggest that IL-4 and IL-13 can regulate the induction of the protective Th2 immune response and intestinal inflammation, both associated with the helminth parasite expulsion [162]. During the Th2 immune response, the cytokines such as IL-4, IL-5, and IL-13 stimulate IgE synthesis [175], inducing mast cell and eosinophil hyperplasia [176], triggering immediate hypersensitivity reactions, and promoting the helminth parasite expulsion from the intestine [177]. However, mast cells and eosinophils are involved in tissue damage, thus promoting the inflammatory response. It suggests that the protective role of the Th2 type immune response is not sufficient facing the challenge against helminth parasite infections, as it contributes

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**7. Conclusion**

We thank the authors who collaborated in the writing of this chapter: Dr. José Luis Muñoz, Dr. Juan Francisco Contreras, Dr. Oscar Gutiérrez, Dra. Paola Trinidad Villalobos, Dra. Viridiana Elizabeth Hernández and Luis Guillermo; as well as the Universities involved: Cuauhtémoc University Aguascalientes, Autonomous University of Nuevo Leon, and University of Guadalajara. We also thank the financial support for chapter publication.
