*3.3. Molecular Adaptations*

The parasite-host relationship is, in most cases, a reciprocal interaction, in which the behavior of the parasite causes feedback in the host and vice versa. Because of this, analyzing this type of feedback mechanism is essential to understand the complex connections between animal behavior, ecology, and parasite evolution [120]. Up to this point, we can reflect on the convenience of using fermentative pathways in the maintenance of parasitic platyhelminths when aerobic respiration (consequently, settling in a place where an abundant supply of oxygen is available) would result in a greater supply of energy and, possibly, a higher metabolic rate. However, when dealing with parasitic forms, it is more important to establish the parasite in a strategic ecological niche that ensures a constant supply of substrates coming from the host (such as liver tissues in the case of flukes or the duodenum in the case of cestodes). Consequently, by having the resources secured, the parasites will concentrate on managing them [121].

One consequence of the foregoing is the parasite's need to interact with its host and be able to maintain its ecological niche by engaging in chemical communication with it. It is not surprising then that the parasite has developed and fine-tuned mechanisms to evade the immune response. For example, it is known that some adult schistosomes can live from three to 10 years in humans, despite the harsh intravascular environment and their constant exposure to the immune system [46]. In fact, it has been possible to verify a registry of patients infected with *S. mansoni* for more than 30 years and the case of a patient infected with *E. granulosus* for 53 years [121].

The feedback between parasitic flatworms and their hosts has been studied using model organisms. For example, the murine experimental model of cysticercosis has made it possible to evaluate the interaction of the host (mice) with the cysticercus of *T. crassiceps* during its proliferation in the peritoneal cavity. This made it possible to describe some of these complex interactions [122], like the importance of the genetic factors of the host (the murine strain used) in the establishment and proliferation of the parasite. Another interesting observation is the importance of the sex of the host as it has been observed that cysticerci grow preferentially in female mice, regardless of the strain of *T. crassiceps*. Apparently, this sexual dimorphism is mediated by hormonal factors, since estrogens favor and androgens hinder the asexual reproduction of cysticerci [123]. Interestingly, when such cysticerci are inoculated into male mice, a feminization phenomenon can be observed in which testosterone levels decrease and estradiol levels increase [124]. The last section of this review will discuss parasite-host feedback in greater detail.
