Protein expression profile of Taenia crassiceps cysticerci related to Th1- and Th2-type responses in the mouse cysticercosis model.

The intraperitoneal cysticercosis model with the Taenia crassiceps ORF strain in female BALB/cAnN mice has been widely used to study the immune response in cysticercosis. During early infection (2 weeks), the host develops a non-permissive Th1 response, whereas during late infection (8 weeks), molecules from the cysticerci induce a Th2 response that is permissive to parasite growth. The modulation of the Th2 response is induced by molecules excreted/secreted by the larval stage of the parasite. However, there is limited information regarding the response of cysticerci to the mouse immunological environment during infection. The proteomic profiles in T. crassiceps ORF cysticerci when faced with the mouse Th1 and Th2 responses were analyzed through two-dimensional gel electrophoresis (2DE), and the differential expression of proteins was evaluated. Thirteen proteins, whose differential expression varied between 70% and 100%, were selected randomly. Protein identification by MALDI-TOF MS and BLAST showed that the proteins were related to folding, signaling, enzymatic activities, cell-movement regulation, cell-cell interactions, motility, carbohydrate metabolism, detoxification, and redox regulation processes. Notably, some of the proteins can act as antigenic-protective molecules and elicit a weak Th1 response; however, most are involved in the avoidance of the immune system, which leads to a Th2 response, or apoptosis. The findings indicate the process by which T. crassiceps cysticerci responds based on the host environment and provides novel insights into the mechanism by which this facilitates its establishment and persistence in the mouse. Furthermore, these proteins could be used as targets for drug and vaccine development.

Taenia solium and Taenia crassiceps: miRNomes of the larvae and effects of miR-10-5p and let-7-5p on murine peritoneal macrophages.

Neurocysticercosis (NCC), a major cause of neurological morbidity worldwide, is caused by the larvae of Taenia solium. Cestodes secrete molecules that block the Th1 response of their hosts and induce a Th2 response permissive to their establishment. Mature microRNAs (miRs) are small noncoding RNAs that regulate gene expression and participate in immunological processes. To determine the participation of Taenia miRs in the immune response against cysticercosis, we constructed small RNA (sRNA) libraries from larvae of Taenia solium and Taenia crassiceps. A total of 12074504 and 11779456 sequencing reads for T. solium and T. crassiceps, respectively, were mapped to the genomes of T. solium and other helminths. Both larvae shared similar miRNome, and miR-10-5p was the most abundant in both species, followed by let-7-5p in T. solium and miR-4989-3p in T. crassiceps, whereas among the genus-specific miRs, miR-001-3p was the most abundant in both, followed by miR-002-3p in T. solium and miR-003a-3p in T. crassiceps. The sequences of these miRs were identical in both. Structure and target prediction analyses revealed that these pre-miRs formed a hairpin and had more than one target involved in immunoregulation. Culture of macrophages, RT-PCR and ELISA assays showed that cells internalized miR-10-5p and let-7-5p into the cytoplasm and the miRs strongly decreased interleukin 16 (Il6) expression, tumor necrosis factor (TNF) and IL-12 secretion, and moderately decreased nitric oxide synthase inducible (Nos2) and Il1b expression (pro-inflammatory cytokines) in M(IFN-γ) macrophages and expression of Tgf1b, and the secretion of IL-10 (anti-inflammatory cytokines) in M(IL-4) macrophages. These findings could help us understand the role of miRs in the host-Taenia relationship.

Fate of uptaken host proteins in Taenia solium and Taenia crassiceps cysticerci.

During the study of host-parasite relationships in taeniid parasite diseases, including cysticercosis and hydatidosis, reports have described the presence of host proteins in the cyst fluid and tissue of metacestodes. However, the fate or role of host elements inside the parasite remains barely explored. After the publication of genomes of four cestode species, it became clear that these organisms possess a limited biosynthetic capability. The initial goal of the present study was to determine if uptaken host proteins could be a source of essential amino acids for cysticerci. To track the utilization of uptaken proteins, we added metabolically labeled IgG-3H and GFP-3H to the culture medium of Taenia crassiceps cysticerci. Incorporation of labeled amino acid was evaluated by fluorography in cysticerci extracts. Our results showed that the use of uptaken proteins by cysticerci as a source of amino acids appeared negligible. Exploring alternative fates for the host proteins, proteomic analysis of the protein matrix in calcareous corpuscles was carried out. Since T. crassiceps does not contain calcareous corpuscles, proteomic analyses were performed in corpuscles of Taenia solium cysticerci. Our results demonstrated that host proteins represented approximately 70% of protein content in the calcareous corpuscles. The presence of the two major uptaken host proteins, namely albumin and IgG, was also demonstrated by Western blot in the matrix of corpuscles. Our findings strongly suggested that the uptake and disposal of host proteins involve calcareous corpuscles, expanding the physiological role of these mineral concretions to a far more important level than previously proposed.

Somatostatin negatively regulates parasite burden and granulomatous responses in cysticercosis.

Cysticercosis is an infection of tissues with the larval cysts of the cestode, Taenia solium. While live parasites elicit little or no inflammation, dying parasites initiate a granulomatous reaction presenting as painful muscle nodules or seizures when cysts are located in the brain. We previously showed in the T. crassiceps murine model of cysticercosis that substance P (SP), a neuropeptide, was detected in early granulomas and was responsible for promoting granuloma formation, while somatostatin (SOM), another neuropeptide and immunomodulatory hormone, was detected in late granulomas; SOM's contribution to granuloma formation was not examined. In the current studies, we used somatostatin knockout (SOM(-/-)) mice to examine the hypothesis that SOM downmodulates granulomatous inflammation in cysticercosis, thereby promoting parasite growth. Our results demonstrated that parasite burden was reduced 5.9-fold in SOM(-/-) mice compared to WT mice (P < 0.05). This reduction in parasite burden in SOM(-/-) mice was accompanied by a 95% increase in size of their granulomas (P < 0.05), which contained a 1.5-fold increase in levels of IFN-γ and a 26-fold decrease in levels of IL-1ß (P < 0.05 for both) compared to granulomas from WT mice. Thus, SOM regulates both parasite burden and granulomatous inflammation perhaps through modulating granuloma production of IFN-γ and IL-1ß.

Helminth infection alters mood and short-term memory as well as levels of neurotransmitters and cytokines in the mouse hippocampus.

UNLABELLED: Helminthic infections are important causes of morbidity and mortality in many developing countries, where children bear the greatest health burden. The ability of parasites to cause behavioral changes in the host has been observed in a variety of host-parasite systems, including the Taenia crassiceps-mouse model. In murine cysticercosis, mice exhibit a disruption in the sexual, aggressive and avoidance predator behaviors. OBJECTIVE: The present study was conducted to characterize short-term memory and depression-like behavior, as well as levels of neurotransmitters and cytokines in the hippocampus of cysticercotic male and female mice. METHODS: Cytokines were detected by RT-PCR and neurotransmitters were quantified by HPLC. RESULTS: Chronic cysticercosis infection induced a decrease in short-term memory in both male and female mice, having a more pronounced effect in females. Infected females showed a significant increase in forced swimming tests with a decrease in immobility. In contrast, male mice showed an increment in total activity and ambulation tests. Serotonin levels decreased by 30% in the hippocampus of infected females whereas noradrenaline levels significantly increased in infected males. The hippocampal expression of IL-4 increased in infected female mice, but decreased in infected male mice. CONCLUSION: Our study suggests that intraperitoneal chronic infection with cysticerci in mice leads to persistent deficits in tasks dependent on the animal's hippocampal function. Our findings are a first approach to elucidating the role of the neuroimmune network in controlling short-term memory and mood in T. crassiceps-infected mice.

Sex-associated expression of co-stimulatory molecules CD80, CD86, and accessory molecules, PDL-1, PDL-2 and MHC-II, in F480+ macrophages during murine cysticercosis.

Macrophages are critically involved in the interaction between T. crassiceps and the murine host immune system. Also, a strong gender-associated susceptibility to murine cysticercosis has been reported. Here, we examined the sex-associated expression of molecules MHC-II, CD80, CD86, PD-L1, and PD-L2 on peritoneal F4/80(hi) macrophages of BALB/c mice infected with Taenia crassiceps. Peritoneal macrophages from both sexes of mice were exposed to T. crassiceps total extract (TcEx). BALB/c Females mice recruit higher number of macrophages to the peritoneum. Macrophages from infected animals show increased expression of PDL2 and CD80 that was dependent from the sex of the host. These findings suggest that macrophage recruitment at early time points during T. crassiceps infection is a possible mechanism that underlies the differential sex-associated susceptibility displayed by the mouse gender.

TLR2 mediates immunity to experimental cysticercosis.

Information concerning TLR-mediated antigen recognition and regulation of immune responses during helminth infections is scarce. TLR2 is a key molecule required for innate immunity and is involved in the recognition of a wide range of viruses, bacteria, fungi and parasites. Here, we evaluated the role of TLR2 in a Taenia crassiceps cysticercosis model. We compared the course of T. crassiceps infection in C57BL/6 TLR2 knockout mice (TLR2⁻/⁻) with that in wild type C57BL/6 (TLR2⁺/⁺) mice. In addition, we assessed serum antibody and cytokine profiles, splenic cellular responses and cytokine profiles and the recruitment of alternatively activated macrophages (AAMφs) to the site of the infection. Unlike wild type mice, TLR2⁻/⁻ mice failed to produce significant levels of inflammatory cytokines in either the serum or the spleen during the first two weeks of Taenia infection. TLR2⁻/⁻ mice developed a Th2-dominant immune response, whereas TLR2⁺/⁺ mice developed a Th1-dominant immune response after Taenia infection. The insufficient production of inflammatory cytokines at early time points and the lack of Th1-dominant adaptive immunity in TLR2⁻/⁻ mice were associated with significantly elevated parasite burdens; in contrast, TLR2⁺/⁺ mice were resistant to infection. Furthermore, increased recruitment of AAMφs expressing PD-L1, PD-L2, OX40L and mannose receptor was observed in TLR2⁻/⁻ mice. Collectively, these findings indicate that TLR2-dependent signaling pathways are involved in the recognition of T. crassiceps and in the subsequent activation of the innate immune system and production of inflammatory cytokines, which appear to be essential to limit infection during experimental cysticercosis.

Substance P signaling contributes to granuloma formation in Taenia crassiceps infection, a murine model of cysticercosis.

Cysticercosis is an infection with larval cysts of the cestode Taenia solium. Through pathways that are incompletely understood, dying parasites initiate a granulomatous reaction that, in the brain, causes seizures. Substance P (SP), a neuropeptide involved in pain-transmission, contributes to inflammation and previously was detected in granulomas associated with dead T. crassiceps cysts. To determine if SP contributes to granuloma formation, we measured granuloma-size and levels of IL-1beta, TNF-alpha, and IL-6 within granulomas in T. crassiceps-infected wild type (WT) mice and mice deficient in SP-precursor (SPP) or the SP-receptor (neurokinin 1, NK1). Granuloma volumes of infected SPP- and NK1-knockout mice were reduced by 31 and 36%, respectively, compared to WT mice (P < .05 for both) and produced up to 5-fold less IL-1beta, TNF-alpha, and IL-6 protein. Thus, SP signaling contributes to granuloma development and proinflammatory cytokine production in T. crassiceps infection and suggests a potential role for this mediator in human cystercercosis.

Neonatal exposure to estradiol induces resistance to helminth infection and changes in the expression of sex steroid hormone receptors in the brain and spleen in adult mice of both sexes.

A single injection of 17beta-estradiol administered to 4-day-old male and female mice increased the cellular immune response, and induced resistance to Taenia crassiceps cysticercosis as well as changes in the expression pattern of progesterone (PR) and estrogen receptor (ER) isoforms in the brain and splenocytes. Regardless of gender, when treated mice reached adulthood, they were highly resistant to infection. Female mice presented early vaginal opening and altered estrous cycles. In male and female mice, the expression of the PR and ER isoforms in the brain was differentially regulated after neonatal exposure to estradiol. Moreover, an increase in the expression of IL-4 and IFN-gamma was found in the serum of experimentally infected neonatally estrogenized animals, which correlated with the observed protection against T. crassiceps infection. In conclusion, early exposure to estradiol permanently modifies immune system activity and sex steroid hormone receptors in the brain, and causes profound changes in sex-associated susceptibility, leading to resistance to helminth parasite infection.

The complex role of pro- and anti-inflammatory cytokines in cysticercosis: immunological lessons from experimental and natural hosts.

Parasitic helminthes have developed complex mechanisms to evade or modulate hosts responses. Studies on cysticercosis are solid, but scarce. The most studied immunological models of cysticercosis are Taenia crassiceps infecting mice and T. solium infecting pigs. These parasites, despite being widely exposed to the host, are able to modulate the host immune system. Taenia metacestodes, much like other helminthes parasites, have developed complicated strategies in order to infect and successfully colonize their hosts. We focus here on the accumulated evidence from experimental models that have been helpful in analyzing and characterizing the host immune response to cysticercosis. Moreover, the mouse model has been used to design rationale vaccine strategies, some of them with promising results. We also discuss recent advances in understanding immune-regulation of cysticercosis. The parasite is able to manipulate the host immune system into supporting its survival by keeping a low inflammatory profile by causing the production of some cysticerci-released products that have immunomodulatory activities, as well as promoting the raise of alternatively activated macrophages. Finally, we delineate, according to recent literature, the likely pathway involved in protection and susceptibility against cysticercosis. As more aspects of the role of different immune and parasite-derived molecules are elucidated, better therapeutic targets may be identified to help treat cysticercosis.

The neuroimmunoendocrine network in the complex host-parasite relationship during murine cysticercosis.

We review here the role that sex steroids play in experimental intraperitoneal Taenia crassiceps cysticercosis of male and female BalbC/AnN mice. Briefly, estrogens favour and androgens hinder the reproduction of cysticerci by at least two main mechanisms: 1) through estradiol tilting the TH2/TH1 immune system balance towards parasite-permissive TH2 response,which is IL-6 dependent mediating P450-aromatase over expression, shunting testosterone towards estradiol and thus creating a positive feed-back loop which progressively favours TH2 response, blocking in turns TH1 and furthers parasite growth; and 2) estrogens and androgens acting directly upon the cysticercus reproductive system, favoring or hindering, respectively, its asexual reproduction. Later infection, when parasite loads are for milliars, male mice become estrogenized, deandrogenized and diminish their copulative, aggressive and social behaviors in association with P450-aromatase testis overexpression. Changes in c-fos expression in different areas of the infected mice brain point to the additional connection of the central nervous system with the infection driven events, which senses and perhaps reacts to infection with behavioral changes. This complex immune-neuro-endocrine network management of parasite loads in murine cysticercosis, and its physiological and behavioral consequences upon the host, may be operative in other infections of mammals. Such complexity may also help to explain the often conflicting results, observed between infections with respect to the role of the host sex, and hints to other avenues of research and strategies for their treatment and control.

Translocation of annexin B1 in response to the stimulation of PMA and ionomycin in cervical cancer cells.

Annexin B1 is a novel member of the annexin superfamily which was isolated from a Cysticercus cellulosae cDNA library. To investigate the physiological roles of annexin B1, we firstly performed immunohistochemical analysis on frozen Cysticercus cellulosae sections and found that annexin B1 was present not only in the tegument of the bladder wall, but also in the host-derived inflammatory layer; In addition, ELISA analysis revealed that annexin B1 could be detected in the cystic fluid of Cysticercus cellulosae and the sera of pigs with cysticercosis. These findings indicated that annexin B1 might be a secretary protein. We further constructed a pEGFP-annexin B1 plasmid and transfected it into SiHa cells. We found that GFP-annexin B1 was stimulated to translocate to the plasma membrane by phorbol 12-myristate 13-acetate (PMA). By contrast, it was induced to distribute at the plasma and nuclear membranes by treatment with calcium ionophore ionomycin. PMA increased annexin B1 membrane binding, which might facilitate exocytosis. Moreover, translocation of the protein to the plasma and nuclear membranes after stimulated by ionomycin, was predicted to be related to an additional function.

Annexin B1 at the host-parasite interface of the Taenia solium cysticercus: Secreted and associated with inflammatory reaction.

Annexin B1 is a novel member of annexin family firstly cloned by immunological screening a Taenia solium cysticercus library. To investigate the histological distribution and physiological role(s) of this protein, we first prepared a specific monoclonal antibody against annexin B1. Western blot analysis indicated that annexin B1 could be detected in cystic fluid of T. solium cysticercus and sera of pigs/humans with cysticercosis. Thus, annexin B1 might belong to the secreted members of annexins. Immunohistochemical analysis revealed that annexin B1 was mainly present in the tegument of bladders, but not in the scolex and neck; it was also detected in the surrounding host-derived layer with granulomatous infiltration. Together with previous, the presented data suggested that the protein inhibited mammalian PLA2 in vitro, and might down regulate host inflammatory responses.

Nitric oxide contributes to host resistance against experimental Taenia crassiceps cysticercosis.

The immune mechanisms that underlie resistance and susceptibility to cysticercosis are not completely understood. In this paper, using susceptible BALB/c mice and resistant STAT6-/-BALB/c mice, we have analyzed the role of nitric oxide (NO) in determining the outcome of murine cysticercosis caused by the cestode Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, IL-5, IL-4, and discrete levels of NO, and remained susceptible to T. crassiceps infection. In contrast, similarly infected BALB/c mice treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) mounted a similar immune response but with lower levels of NO and harbored nearly 100% more parasites than N(omega)-nitro-D-arginine methyl ester (D-NAME, inactive enantiomer)-treated mice. To further analyze the role of NO in murine cysticercosis, we treated STAT6-/-male mice (known to be highly resistant to T. crassiceps) with L-NAME during 8 weeks of infection. As expected, STAT6-/-mice mounted a strong Th1-like response, produced high levels of IgG2a, IFN-gamma, and IL-17, whereas their macrophages displayed increased transcripts of tumor necrosis factor (TNF)-alpha as well as inducible nitric oxide synthase (iNOS) and efficiently controlled T. crassiceps infection. However, STAT6-/-male mice receiving L-NAME mounted a similar immune response but with lower iNOS transcripts concomitantly with decreased levels of NO in sera and displayed significantly higher parasite burdens. These findings suggest that macrophage activation and NO production are effector mechanisms that importantly contribute in host resistance to T. crassiceps infection. The immune mechanisms that underlie resistance and susceptibility to cysticercosis are not completely understood. In this paper, using susceptible BALB/c mice and resistant STAT6-/-BALB/c mice, we have analyzed the role of nitric oxide (NO) in determining the outcome of murine cysticercosis caused by the cestode Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, IL-5, IL-4, and discrete levels of NO, and remained susceptible to T. crassiceps infection. In contrast, similarly infected BALB/c mice treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) mounted a similar immune response but with lower levels of NO and harbored nearly 100% more parasites than N(omega)-nitro-d-arginine methyl ester (D-NAME, inactive enantiomer)-treated mice. To further analyze the role of NO in murine cysticercosis, we treated STAT6-/-male mice (known to be highly resistant to T. crassiceps) with L-NAME during 8 weeks of infection. As expected, STAT6-/-mice mounted a strong Th1-like response, produced high levels of IgG2a, IFN-gamma, and IL-17, whereas their macrophages displayed increased transcripts of tumor necrosis factor (TNF)-alpha as well as inducible nitric oxide synthase (iNOS) and efficiently controlled T. crassiceps infection. However, STAT6-/-male mice receiving L-NAME mounted a similar immune response but with lower iNOS transcripts concomitantly with decreased levels of NO in sera and displayed significantly higher parasite burdens. These findings suggest that macrophage activation and NO production are effector mechanisms that importantly contribute in host resistance to T. crassiceps infection.

Acute cysticercosis favours rapid and more severe lesions caused by Leishmania major and Leishmania mexicana infection, a role for alternatively activated macrophages.

Parasitic helminths have developed complex mechanisms to modulate host immunity. In the present study we found that previous infection of mice with the cestode Taenia crassiceps favours parasitemia and induces larger cutaneous lesions during both Leishmania major and Leishmania mexicana co-infections. Analysis of cytokine responses into draining lymph nodes indicated that co-infection of T. crassiceps-Leishmania did not inhibit IFN-gamma production in response to Leishmania antigens, but significantly increased IL-4 production. Additionally, anti-Leishmania-specific IgG1 antibodies and total IgE increased in co-infected mice, whereas, IgG2a titers remained similar. Macrophages from Taenia-infected mice displayed increased mRNA transcripts of arginase-1, Ym1, and Mannose Receptor, as well as greater production of urea (all markers for an alternate activation state) compared to macrophages from Leishmania-infected mice. In contrast, lower mRNA transcripts for IL-12p35, IL-12p40, IL-23p19, and iNOS were detected in macrophages obtained from cestode-infected mice compared to uninfected and Leishmania-infected mice after LPS stimulation. The presence of cestode also generated impaired macrophage anti-leishmanicidal activity in vitro, as evidenced by the inability of these macrophages to prevent Leishmania growth compared to macrophages from uninfected mice. This was observed despite the fact that both groups of cells were exposed to IFN-gamma. Flow cytometry showed high IFN-gammaR expression on Taenia-induced macrophages. Thus, lack of response to IFN-gamma is not associated with the absence of its receptor. Our data suggest that cestode infection may favour Leishmania installation by inducing alternatively activated macrophages rather than inhibiting Th1-type responses.

Positive reaction for cysticercosis and multicentric anaplastic oligoastrocytoma.

INTRODUCTION: An unusual case of positive immunological testing for cysticercosis in the cystic fluid obtained from an anaplastic oligoastrocytoma is presented. CASE REPORT: A 15-year-old boy was admitted with multiple brain lesions. The biggest was a cyst with a mural node and neurocysticercosis was suspected. In order to relieve intracranial pressure, the cyst was punctured and the immunological testing for cysticercosis was positive, reinforcing the clinical suspicion and leading to a clinical trial with albendazole and steroids. As the patient deteriorated the cystic lesion was removed and the diagnosis of anaplastic oligoastrocytoma was established. A second lesion was eventually approached and the histopathological diagnosis of both specimens concurred. DISCUSSION: Although some authors believe that chronic inflammatory changes following neurocysticercosis could induce the formation of brain tumors, this association may be a mere coincidence. In our case no clinical evidence of a prior infestation by Cysticercus was found. In fact, an exhaustive examination of the specimens did not reveal any areas of inflammatory reaction. We believe that the similarity of the glioma and cysticercosis antigens may be the cause of the positive reactions in the cystic fluid.

Host gender in parasitic infections of mammals: an evaluation of the female host supremacy paradigm.

A review of current literature on mammalian hosts' sexual dimorphism (SD) in parasitic infections revealed that (1) it is a scarcely and superficially studied biological phenomenon of considerable significance for individual health, behavior, and lifestyles and for the evolution of species; (2) there are many notable exceptions to the rule of a favorable female bias in susceptibility to infection; (3) a complex network of molecular and cellular reactions connecting the host's immuno-neuroendocrine systems with those of the parasite is responsible for the host-parasite relationship rather than just an adaptive immune response and sex hormones; (4) a lack of gender-specific immune profiles in response to different infections; (5) the direct effects of the host hormones on parasite physiology may significantly contribute to SD in parasitism; and (6) the need to enrich the reductionist approach to complex biological issues, like SD, with more penetrating approaches to the study of cause-effect relationships, i.e., network theory. The review concludes by advising against generalization regarding SD and parasitism and by pointing to some of the most promising lines of research.

Immunolocalization of the 150 kDa protein in cyst fluid of Taenia solium metacestodes.

The 150 kDa protein of cyst fluid (CF) of Taenia solium metacestodes was purified by ammonium sulfate fractionation and Superose 6 HR gel filtration chromatography. The purified protein consisted of three subunits (15, 10 and 7 kDa proteins), which were analyzed with the use of a 7.5-15% gradient sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunofluorescence study was carried out by using immunize specific polyclonal antibody. Positive reactions were noticed at bladder walls, calcareous corpuscles, granules of cyst fluid and some host tissue surrounding the bladder wall of the metacestodes. These results suggest that the 150 kDa protein was secreted into host tissues, inducing immune responses in the host, and it may play important roles in the cellular physiology of the parasites.

Remote sensing of intraperitoneal parasitism by the host's brain: regional changes of c-fos gene expression in the brain of feminized cysticercotic male mice.

Experimental intraperitoneal Taenia crassiceps cysticercosis in mice exhibits distinct genetical, immunological and endocrinological features possibly resulting from the complex interactive network of their physiological systems. Very notable is the tendency of parasites to grow faster in hosts of the female sex. It is also remarkable in the feminization process that the infection induces in chronically infected male mice, characterized by their estrogenization, deandrogenization and loss of sexual and aggressive patterns of behaviour. The proto-oncogene c-fos is a sex steroid-regulated transcription factor gene, expressed basally and upon stimulation by many organisms. In the CNS of rodents, c-fos is found expressed in association to sexual stimulation and to various immunological and stressful events. Hence, we suspected that changes in c-fos expression in the brain could be involved in the feminization of the infected male mice. Indeed, it was found that c-fos expression increased at different times during infection in the hypothalamus, hippocampus, less so in the preoptic area and cortex, and not in several other organs. The significant and distinctive regional changes of c-fos in the CNS of infected mice indicate that the brain of the host senses intraperitoneal cysticercosis and may also announce its active participation in the regulation of the host-parasite relationship. Possibly, the host's CNS activity is involved in the network that regulates the estrogenization and deandrogenization observed in the chronically infected male mice, as well as in the behavioural and immunological peculiarities observed in this parasitic infection.