Bakiri et al and VSP mRNA levels after infection of mice with cysts lead to an antigenic reset of the parasite, which appears to be as- sociated with excystation [48]. In this respect, the VSP H7 type has to be regarded as a predominant variant of Giardia lamblia clone GS/M-83-H7 that (re-)emerges during early- stage infection and may contribute to an optimal establish- ment of the parasite within the intestine of the experimental murine host [48]. In summary, the Th2 response seems to be a host reaction, induced under the parasites’ influence. It may permit the migration of parasites under the skin, in lymphatic ways and into some parenchimatous organs. In a few cases, this response may be induced in some developing phases, such as in case of excystation (which is also a kind of barrier penetration) or epithelial inoculation of giardiasis. Taken together, these data indicate that urticarial symptoms may be related to the larval stage or hostile tissue penetra- tion, but not necessarily only to the presence of parasitic infection in the human organism. This may explain the lack of clear evidence regarding the correlation between the para- sitic diseases and the urticaria development. Eosinophils as barrier perforators: are they double game players? In spite of the humoral mechanisms, there is evidence of im- portant parasite-induced effects on innate cell types, particu- larly mast cells and eosinophils. According to Maizels et al., the sum effect of these changes to host reactivity is to create an “anti-inflammatory environment”, which is most favor- able to parasite survival [15, 33]. However in our opinion, the role of eosinophils is more complex. The eosinophils like the complement system can induce increased cell membrane permeability [49, 50]. This eosinophil-induced role is also shown on various biologic barriers, including the parasite surfaces. This effect is called “frustrated phagocytosis” [48, 51]. Thus, Kaji et al. reported about a case of urticaria, eo- sinophilic cholecystitis and a simultaneous onset with peri- carditis after an ascaris infection [52]. Infection from Angio- strongylus cantonensis is generally associated with damage of blood-brain barrier and neurological disorders, which is assumed to be a consequence of eosinophilic meningitis [50, 53]. Besides the host-influence, eosinophils migration close to parasites could be also a strategic step induced even from the parasite, leading to the allergic symptoms. While a hype- reosinophilia is an argument in favor of a progressive toxo- cara infection, high total IgE level is considered a hallmark of visceral infections by parasites [54, 55]. Furthermore, anisakis larvae extract exercises a chemotactic effect for eo- sinophils [56]. In this context, alive L3 larvae can exhibit the main hyperergic response in the duodenum, decelerating their transit into the successive parts of intestinum, but also inducing the transit into the tissues outside the duodenal lu- men [57]. In other words, since parasites affect the behavior J Clin Med Res • 2010;2(6):247-255 traits with selectively benefit the parasite, rather than causing a general alteration of the host behavior, the induction of the urticaria and the atopic phenotype might be only an efficient or hopeless larval attempt to find the suitable host to produce eggs. The IgE-response, the eosinophilic chemotaxis, or the general itching cannot be only host defenses, but also larval attempts to destroy hostile barriers to search for the missed suitable hostile environments. Taken together, these findings indicate that eosinophils as biological barrier perforators are implicated under the simultaneous influence of the host and parasites in a double game. This hypothesis is supported for example by the presence of local eosinophil infiltration in the skin when Dracunculus medinensis larvae emerge from the inferior limbs in the ponds water [58]. In these circum- stances, the eosinophils could help parasites to destroy the skin integrity, because in this stage dracunculae larvae can be developed only within thermocyclops living in ponds. This also demonstrates that helminths display highly complex life cycles in which the establishment of adults or larvae within host target organs as well as the transition of one develop- mental stage to the following is influenced by host-derived factors [22]. Parasites as efficient manipulators of the host behavior The parasite-manipulated involvement of host immune mechanisms supports the opinion that parasites are efficient manipulators of the host behavior (a further dimension of the parasite influence on the host reaction) [57]. The parasitic ability to affect the behavior of infected host has been docu- mented and reviewed by different authors [13-16, 59, 60]. Although changes in the behavior of infected hosts do occur for pathogens with direct life cycle, they are most commonly recorded in the intermediate hosts of parasites with com- plex life cycle. In the simplest case, the changes in behavior increase rates of contact between infected and susceptible conspecific hosts, whereas in the more complex cases fairly sophisticated manipulations of the host’s behavioral reper- tory are achieved [59-62]. In this context, because sexual reproduction of Toxoplasma gondii can be accomplished only in felines, there are strong selective pressures on the parasite to evolve mechanisms to enhance transmission from the intermediate host to the definitive feline host and thereby complete its life cycle. The predilection of Toxoplasma gon- dii for the brain of its intermediate host places it in a privi- leged position to cause such manipulation [62]. Ferreira et al. recently demonstrated that the host cell transcriptome, in- cluding the expression of distinct host cell genes, can trigger bradyzoite development and cyst formation, strongly indi- cating that the complex cellular environment may govern the developmental differentiation of this protozoa [63]. More- over, the pattern of histone H3 arginine methylation distin- guishes certain promoters, illustrating the complexity of the histone modification machinery in toxoplasmosis [64, 65]. 250 Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press™ | www.jocmr.org