Behavioral Manipulation by Toxoplasma gondii: Does Brain Residence Matter?

The protozoan parasite Toxoplasma gondii infects a wide range of intermediate hosts. The parasite produces brain cysts during the latent phase of its infection, in parallel to causing a loss of innate aversion in the rat host towards cat odors. Host behavioral change presumably reflects a parasitic manipulation to increase predation by definitive felid hosts, although evidence for increased predation is not yet available. In this opinion piece, we propose a neuroendocrine loop to explain the role of gonadal steroids in the parasitized hosts in mediating the behavioral manipulation. We argue that the presence of tissue cysts within the host brain is merely incidental to the behavioral change, without a necessary or sufficient role.

A fish model for the study of the relationship between neuroendocrine and immune cells in the intestinal epithelium: Silurus glanis infected with a tapeworm.

Immunohistochemical, immunofluorescence and ultrastructural studies were conducted on a sub-population of 20 wels catfish Silurus glanis from a tributary of the River Po (Northern Italy). Fish were examined for the presence of ecto- and endo-parasites; in the intestine of 5 fish, 11 specimens of cestode Glanitaenia osculata were noted and was the only helminth species encountered. The architecture of intestine and its cellular features were nearly identical in either the uninfected S. glanis or in those harboring G. osculata. Near the site of worm's attachment, mucous cells, several mast cells (MCs), few neutrophils and some endocrine cells (ECs) were found to co-occur within the intestinal epithelium. MCs and neutrophils were abundant also in the submucosa. Immunohistochemical staining revealed that enteric ECs were immunoreactive to met-enkephalin, galanin and serotonin anti-bodies. The numbers of ECs, mucous cells and MCs were significantly higher in infected wels catfish (Mann-Whitney U test, p < 0.05). Dual immunofluorescence staining with the biotinylated lectin Sambucus nigra Agglutinin and the rabbit polyclonal anti-met-enkephalin or anti-serotonin, with parallel transmission electron microscopy, showed that ECs often made intimate contact with the mucous cells and epithelial MCs. The presence of numerous MCs in intestinal epithelium shows S. glanis to be an interesting model fish to study processes underlying intestinal inflammation elicited by an enteric worm. Immune cells, ECs and mucous cells of the intestinal epithelium have been described at the ultrastructural level and their possible functions and interactions together will be discussed.

Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance.

C57BL/6 mice infected with Trypanosoma cruzi, the causal agent of Chagas' disease, develop severe thymocyte depletion paralleled by an inflammatory syndrome mediated by tumor necrosis factor-alpha (TNF-alpha). The exacerbated inflammatory reaction induces the activation of hypothalamus-pituitary-adrenal (HPA) axis with the consequent release of corticosterone (CT) into the circulation as a protective response. Thymocyte apoptosis has been related to a rise in TNF-alpha and CT levels, and both mediators are increased in T. cruzi-infected C57BL/6 mice. The depletion of immature CD4(+)CD8(+) thymocytes by apoptosis following infection with the parasite was still present in mice defective in both types of TNF-receptors (double knockout). However, thymic atrophy was prevented by adrenalectomy combined with RU486 administration, demonstrating that this is a CT-driven phenomenon. Our results put emphasis on the importance of an appropriated immuno-endocrine balance during T. cruzi infection and show that functional deviations in the immuno-endocrine equilibrium have profound effects on the thymus and disease outcome.

Histopathology and ultrastructure of Platichthys flesus naturally infected with Anisakis simplex s.l. larvae (Nematoda: Anisakidae).

The histopathology, ultrastructure, and immunohistochemistry of the alimentary canal of flounder Platichthys flesus (L.), naturally infected with the nematode Anisakis simplex s.l. (Rudolphi 1809) from the River Forth (Scotland), were investigated and described. Eight of the 16 flounders were infected with A. simplex s.l. larvae (L3); parasites were encapsulated by serosa on the external surface of the host's digestive tract (intensity of infection 1-8 parasites per host), although nematode larvae were found encysted under the peritoneal visceral serosa of the host spleen and liver and, occasionally, in the liver parenchyma (intensity of infection 3-10 parasites per host). In all sites, different structural elements were recognized within the capsule surrounding larvae. Among the epithelial cells of the intestine of 5 flounders with larvae encysted on external surface of the gut, the presence of several rodlet cells (RCs) was observed. Furthermore, often the occurrence of macrophage aggregates (MAs) was noticed in infected liver and spleen, mainly around the parasite larvae. Eight neuropeptide antisera were tested with immunohistochemistry methods on gut sections of 4 P. flesus infected with extraintestinal nematodes. Sections from the gut of 5 uninfected flounder were used for comparative purposes. In the tunica mucosa of parasitized P. flesus, several endocrine epithelial cells were immunoreactive to anti-CCK-39 (cholecystokinin 39) and -NPY (neuropeptide Y) sera; furthermore, in the myenteric plexus, a high number of neurons were immunoreactive to antibombesin, -galanin, and several to -NPY and -PHI (peptide histidine isoleucine) sera.

Immunoneuroendocrine interactions in Chagas disease.

We investigated immunoneuroendocrine interactions in vivo and in vitro following infection by Trypanosoma cruzi, the causative agent of Chagas disease. In a first set of experiments, we studied the hypothalamus-pituitary-adrenal axis. Nests of parasites were seen in the adrenal gland, whereas T. cruzi-specific PCR gene amplification product was found in both the adrenal and pituitary glands of infected mice. These endocrine glands also revealed alterations including vascular stasis, increase in the deposition of extracellular matrix (ECM), as well as T cell and macrophage infiltration. Functionally, we found a decrease in corticotrophin-releasing hormone and an increase in corticosterone contents, in hypothalamus and serum, respectively, whereas no significant changes were seen in serum adrenocortricotropic hormone of infected animals. Nevertheless, the serum levels of interleukin-6 (known to directly stimulate glucocorticoid secretion) were increased, as compared to controls. Considering the presence of T cells within the nervous tissue of chagasic animals, we performed a number of in vitro experiments co-culturing spleen-derived T cells from control or infected mice, with neuronal cells (being or not being directly infected in vitro). In particular, we looked for ECM-mediated interactions, known to affect T cell migration. We found an increase in ECM deposition in infected cultures, as compared to controls. Moreover, adhesion of T cells was enhanced when neuronal cells were infected in vitro, or when T cells were derived from T. cruzi-infected mice, events that could be abrogated with anti-ECM antibodies. Together, the data summarized above clearly reveal that neuroendocrine axes are altered in experimental Chagas disease.

Effect of Pomphorhynchus laevis (Acanthocephala) on putative neuromodulators in the intestine of naturally infected Salmo trutta.

Immunohistochemical and pathological studies were carried out on the digestive tract of parasitized and uninfected specimens of Salmo trutta (L.). A total of 124 brown trout were collected on several occasions from 3 tributaries of the Brenta River, northern Italy. Twenty-eight individuals of S. trutta (22.6%) were parasitized with Pomphorhynchus laevis (Miller, 1776). The occurrence of P. laevis in the trout gut significantly increased the number of endocrine cells immunoreactive to calcitonin gene-related peptide (CGRP), beta-endorphin, met-enkephalin, neuropeptide Y (NPY) and Substance P (SP) antisera. Moreover, bombesin-, cholecistokinin-8- (CCK-8), leu-enkephalin- and serotonin- (5-HT)-like immunoreactive cells were less numerous in the intestine of the parasitized brown trout. A strong positive immunoreactivity was observed in nerve fibres and neurones of the myenteric plexus of the parasitized fish; the antisera involved in this positive reactivity were bombesin, met-enkephalin, SP and vasoactive intestinal peptide (VIP). More neurones immunoreactive to anti-CGRP and anti-5-HT sera were noted in the myenteric plexus and in the inner layer of the tunica muscularis of the infected fish. Most of the above-mentioned neuromodulators are known to control gut motility, digestive/absorptive processes, as well as the immune response. The changes induced by parasites in the neuroendocrine system of the brown trout are discussed.