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(a) Focal infiltration of inflammatory mononuclear cells in the cerebrum; (b) lymphoid hyperplasia in intestinal submucosa; (c) hepatic granuloma; (d) E. cuniculi spores in enterocytes (arrow). All HE; 400x.

(a) Focal infiltration of inflammatory mononuclear cells in the cerebrum; (b) lymphoid hyperplasia in intestinal submucosa; (c) hepatic granuloma; (d) E. cuniculi spores in enterocytes (arrow). All HE; 400x.

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This study was performed to evaluate pathology of experimental Encephalitozoon cuniculi (Iraqi isolate) infection in normal and immunosuppressed mice. Pathological changes were not seen in negative control mice while secondary bacterial infections were noted in the lungs, kidneys, and heart of mice given dexamethasone. Typical E. cuniculi infection...

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... Similar decrease in number of lymphocytes subpopulations in the blood in immunodeficient mice were obtained in the other studies [14]. ...
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It is known that peptides inhibit the enzymes of viruses and are able to penetrate into cells by their embedding in the cell membrane, as a result of which the penetration of viruses into the host cell is blocked, which makes it possible to consider peptides as an alterna tive to antiviral drugs. In this regard, the demand for immune-boosting nutraceuticals and functional foods containing biologically active peptides is growing. The immunomodulating effect of the peptides were studied on the mice of the BALb/c line that suffered from experimentally induced immunodeficiency; the mice got injections of peptides isolated from the bursa of Fabricius (bursal sac) of broiler chickens. 5 groups of BALb/c mice were formed. The animals of the 1st group (control one) received physiological saline per os as a placebo, animals of the 2 nd group got bursal peptides per os at a dose of 0.02 mg/kg per body weight, the mice of 3 rd group (immunosuppressed) got saline per os as a placebo, the 4 th group (immunosuppressed) was administered the bursal peptides per os at a dose of 0.02 mg/kg of body weight, the 5 th group was held as the control one (immunosuppressed group). Blood for tests was taken on days 1, 7 and 14 of the experiment. The functional activity of neutrophils was determined by the method of spontane ous and induced chemiluminescence. Among the immudepressive animals (the 3 rd group) on the 7 th day the researchers observed a decrease in CD3+ by 55.3%, CD22+ by 83.7%, CD3+CD4+ by 51.9% and CD3+CD8+ by 54.6% in comparison with the intact (the 1st group). Administration of peptides to immunosuppressed mice (the 4 th group) increases the number of subpopulations of CD3+ lymphocytes by 126.6%, CD22+ by 381.6%, CD3+CD4+ by 8.9% and CD3+CD8+ by 81.8% compared to immunosuppressed ani mals, receiving saline per os as a placebo (group 3). Similar results were obtained on the 14th day of the experiment. On the basis of the performed studies, it can be argued that the immunocompetent organs of broiler chickens (bursa of Fabricius) are a promising source of immunotropic peptides.).
... After ingestion, spores migrate to the intestinal epithelium and establish a primary focus of infection, although they may also infect resident inflammatory cells in the digestive tract, such as macrophages and intraepithelial lymphocytes. Finally, spores reach the brain and kidneys, either via blood, or the lymphatic system, where infection results in severe granulomatous meningoencephalitis and interstitial and granulomatous nephritis in immunosuppressed and immunocompetent individuals [7]. Natural and experimental E. cuniculi infections have shown that infectious spores tend to form well-circumscribed microgranulomas in the brain, whereas within the kidneys, they exhibit a more diffuse pattern [8,9]. ...
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Encephalitozoon cuniculi is a fungi-related, obligate, zoonotic, spore-forming intracellular eukaryotic microorganism. This emerging pathogen causes granulomas to form in the brain and kidneys of infected individuals. The objective of the current study was to detect the distribution of TNF-α- and IL-4-positive cells using immunohistochemistry within these granulomas in both infected immunocompetent (group A) and immunosuppressed (group B) New Zealand white rabbits. In the brain, labeled TNF-α immune cells were mainly located in the granuloma peripheries in group B. Granulomas examined in the kidneys of groups A and B were TNF-α positive, but were significantly different (p < 0.001) when compared with the brain. IL-4-producing immune cells in the brain and kidneys were disseminated within granulomas in groups A and B; however, no significant difference (p > 0.05), was observed. IL-4 positive cells were more numerous in brain sections of group B and differed significantly (p < 0.05) when compared with kidneys. Granulomas were not observed in control animals (groups C and D). In conclusion, we identified TNF-α positive cells in both the brain and kidneys of immunocompetent and immunosuppressed animals; IL-4 positive cells were numerous in the brains of immunosuppressed rabbits; however, in terms of percentage were numerous in the brains of immunocompetent rabbits. Immunosuppression appeared to stimulate a change in the cellular phenotype of Th1- to Th2-like granulomas in the brain and kidneys via an unknown mechanism. Expression of pro- and pre-inflammatory cytokines in microsporidian granulomas suggests a mechanism by which E. cuniculi evades the immune response, causing more severe disease. These results increase our understanding of TNF-α and IL-4-positive cells within the E. cuniculi granuloma microenvironment.
... bieneusi isolates, which supports the zoonotic transmission of some of its genotypes from animals [37] . Others revealed that animals may represent a major source for spore transmission of opportunistic infection in humans [38] . ...
... Clinical signs comprise ataxia, torticollis, and uncontrolled rolling behavior along its long axis [4]. The encephalitozoonosis is a zoonotic and emerging disease that can infect both immunocompetent and immunocompromised individuals; thus, E. cuniculi has gained worldwide attention owing to its importance as both human and animal pathogen [5]. Most studies of E. cuniculi infection have investigated immunocompetent and immunosuppressed strains of rodents [6], where limited studies have been conducted in rabbits, the definitive host [7]. ...
... Encephalitozoon cuniculi is one of the most common microsporidian species, in humans or animals. It is considered to be an emerging zoonotic and opportunistic pathogen in immunocompromised as well as immunocompetent individuals [2]. Spores of E. cuniculi can survive in macrophages, spread throughout the host, and cause lesions in organs of the urinary, digestive, respiratory, and nervous systems [3]. ...
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Here, we have investigated the possible effect of B-1 cells on the activity of peritoneal macrophages in E. cuniculi infection. In the presence of B-1 cells, peritoneal macrophages had an M1 profile with showed increased phagocytic capacity and index, associated with the intense microbicidal activity and a higher percentage of apoptotic death. The absence of B-1 cells was associated with a predominance of the M2 macrophages, reduced phagocytic capacity and index and microbicidal activity, increased pro-inflammatory and anti-inflammatory cytokines production, and higher percentual of necrosis death. In addition, in the M2 macrophages, spore of phagocytic E. cuniculi with polar tubular extrusion was observed, which is an important mechanism of evasion of the immune response. The results showed the importance of B-1 cells in the modulation of macrophage function against E. cuniculi infection, increasing microbicidal activity, and reducing the fungal mechanisms involved in the evasion of the immune response.
... Although the disease is very common in pet rabbits, little is known about the exact pathophysiology of E. cuniculi infection [8]. To date, most of the immunological studies have been performed in experimental models, e.g. in rats, and only rarely in the natural rabbit host [9,10]. In such a context, accurate description of the whole proteome, i.e. description of both microsporidian proteins and host proteins that are involved in the response to E. cuniculi infection, represents a novel approach to expand our understanding of this infectious agent [11]. ...
... It represents a major health issue for rabbits in which seroprevalence rates have been estimated by 37-68% of the pet population [24]. Although it has been largely studied for pathophysiology and immunology in experimental rodent models [9,10] and, to a limited point, in some experimentallyinfected rabbits [8,25], additional insights are needed in naturally-infected hosts [26]. In the current study, we applied new mass spectrometry (MS) tools to comprehensively explore proteomic changes during E. cuniculi infection in naturally-infected rabbits. ...
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Encephalitozoon cuniculi is a microsporidian species which can induce subclinical to serious disease in mammals including rabbits, a definitive natural host. The pathophysiology of infection has not been comprehensively elucidated. In this exploratory study, we utilized two mass spectrometry approaches: first, the analysis of the humoral response by profiling the microsporidian antigens as revealed by Western blot screening, and second, implementing the iTRAQ®-labeling protocol to focus on the changes within the host proteome during infection. Seven E. cuniculi proteins were identified at one-dimensional gel regions where specific seropositive reaction was observed by Western blot, including polar tube protein 3, polar tube protein 2, and for the first time reported: heat shock related 70kDa protein, polysaccharide deacetylase domain-containing protein, zinc finger protein, spore wall and anchoring disk complex protein EnP1, and translation elongation factor 1 alpha. In addition, there was a significant increase of nine host proteins in blood samples from E. cuniculi-diseased rabbits in comparison with non-diseased control subjects undergoing various inflammatory processes. This included serum paraoxonase, alpha-1-antiproteinase F precursor and alpha-1-antiproteinase S-1 which have presumptive catalytic activity likely related to infection control, and cystatin fetuin-B-type, an enzyme regulator that has been poorly studied to date. Notably, 11 proteins were found to be statistically increased in rabbits with neurological versus renal clinical presentation of E. cuniculi infection. Overall, this novel analysis based on mass spectrometry has provided new insights on the inflammatory and humoral responses during E. cuniculi infection in rabbits.
... Infected rabbits eliminate the spores in urine and feces; thus, infection of the host generally occurs after the ingestion of water or food contaminated with infective spores [5]. Encephalitozoon cuniculi is considered to be an emergent, zoonotic, and opportunistic pathogen in immunocompetent and immunocompromised individuals [6,7]. The spores infect enterocytes and, perhaps through Peyer's patches or interepithelial lymphocytes, spread to the bloodstream or the lymphatic system, reaching the brain, kidney, liver, and other organs. ...
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This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi) in farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited clinical signs of this zoonotic emerging disease, like torticollis, ataxia, paresis, circling, and rolling. Samples of brain, kidney, and liver were examined for histology lesions. For the first time the lesions caused by E. cuniculi were graded according to their severity (I, II, and III) and the size of the granulomas (Types A, B, and C). The main cerebral injuries were Grade III, coinciding with the presence of Type C granulomas. The cerebral lesions were located in the cortex, brain stem, and medulla. The renal lesions were also Grade III distributed throughout cortex and renal medulla, with no granuloma formation. The involvement of hypersensitivity Types III and IV is suggested. All of the rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this zoonotic and emerging pathogen is widely distributed among animals intended for human consumption. We believe this work could be used as a guide when examining E. cuniculi and will provide direction to confirm the diagnosis of this pathogen.
... Also, these means will be very efficient not only to fight the mosquito sand fly vector of such diseases but also to combat the parasite tanks such as rats and stray dogs who are increasingly responsible for many emerging zoonoses [31,32]. ...
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Cutaneous leishmaniases (CL) are endemic in Morocco. They are common in the human population in different localities such as Aichoun in Sefrou province, Morocco. This study was carried out in Aichoun locality from April to October 2012 in order to study the spatiotemporal trends of the main Leishmania phlebotomine vectors in this focus. Overall, 1171 sand flies, belonging to four species, were collected by sticky traps. Phlebotomus sergenti was the predominant species (78.4%) followed by Ph. perniciosus (10.5%), Ph. papatasi (7.94%), and Ph. longicuspis (3.16%). Sandflies were active during 6 months (May-October). Ph. sergenti, Ph. perniciosus, and Ph. papatasi displayed a bimodal distribution with a first peak in July and a second peak in September, while Ph. longicuspis showed a monophasic trend with a peak in August. The high abundance and the lengthy period of activity of Ph. sergenti and Ph. perniciosus, vectors of L. tropica and L. infantum, respectively, are a cause for concern as they indicate the high potential risk of Leishmania transmission in the studied areas.
Chapter
Encephalitozoon cuniculi is a pathogen with a worldwide distribution, belonging to the phylum Microsporidia (kingdom Fungi), which infects rabbits (Oryctolagus cuniculus) and several other animals, including humans. Encephalitozoon cuniculi was the first microsporidium to be described in mammals. The global population of rabbits is exposed to this pathogen, and, although most infections are subclinical, E. cuniculi can cause severe illness, with neurological, ocular, and renal involvement. In humans, especially in immunocompromised individuals, E. cuniculi has been implicated as an opportunistic agent. Spore proliferation and migration can be reduced by treatment, and preventive antimicrosporidial medications may be considered. Different control measures are necessary for decreasing the spread of E. cuniculi, not only to other rabbits but also to humans. This chapter provides a review of the literature regarding the pathogen E. cuniculi, infection epidemiology, pathogenesis, lesions and clinical signs of disease, and diagnostic and control methods including treatment and prevention of encephalitozoonosis.