Total joint arthroplasty is a commonly used surgical procedure in orthopedics. Revision surgeries are required in >10% of patients mainly because of prosthetic joint infection caused by bacteria or aseptic implant loosening caused by chronic inflammation. Encephalitozoon cuniculi is a microsporidium, an obligate intracellular parasite, capable of exploiting migrating proinflammatory immune cells for dissemination within the host. We used molecular detection methods to evaluate the incidence of E. cuniculi among patients who had total hip or knee arthroplasty revision. Out of 49 patients, E. cuniculi genotypes I, II, or III were confirmed in joint samples from 3 men and 2 women who had implant loosening. Understanding the risks associated with the presence of microsporidia in periprosthetic joint infections is essential for proper management of arthroplasty. Furthermore, E. cuniculi should be considered a potential contributing cause of joint inflammation and arthrosis.
- MeSH
- Encephalitozoon cuniculi * genetika MeSH
- encephalitozoonóza * epidemiologie MeSH
- lidé MeSH
- Microsporidia * genetika MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or effective treatment. Although it is known from human cases and animal models that CD4+ T cells play a role in curbing Cryptosporidium, the role of CD8+ T cells remains to be defined. Using a Cryptosporidium tyzzeri mouse model, we show that gut-resident CD8+ intraepithelial lymphocytes (IELs) confer resistance to parasite growth. CD8+ IELs express and depend on the ligand-dependent transcription factor aryl hydrocarbon receptor (AHR). AHR deficiency reduces CD8+ IELs, decreases their cytotoxicity, and worsens infection. Transfer of CD8+ IELs rescues severely immunodeficient mice from death following Cryptosporidium challenge. Finally, dietary supplementation of the AHR pro-ligand indole-3-carbinol in newborn mice promotes resistance to infection. Therefore, common dietary metabolites augment the host immune response to cryptosporidiosis, protecting against disease.
Microsporidia are pathogenic organism related to fungi. They cause infections in a wide variety of mammals as well as in avian, amphibian, and reptilian hosts. Many microsporidia species play an important role in the development of serious diseases that have significant implications in human and veterinary medicine. While microsporidia were originally considered to be opportunistic pathogens in humans, it is now understood that infections also occur in immune competent humans. Encephalitozoon cuniculi, Encephalitozoon intestinalis, and Enterocytozoon bieneusi are primarily mammalian pathogens. However, many other species of microsporidia that have some other primary host that is not a mammal have been reported to cause sporadic mammalian infections. Experimental models and observations in natural infections have demonstrated that microsporidia can cause a latent infection in mammalian hosts. This chapter reviews the published studies on mammalian microsporidiosis and the data on chronic infections due to these enigmatic pathogens.
- MeSH
- Enterocytozoon * MeSH
- feces mikrobiologie MeSH
- lidé MeSH
- Microsporidia * genetika MeSH
- perzistentní infekce MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Background: Microsporidia of the genus Encephalitozoon are usually associated with severe infections in immunodeficient hosts while, in immunocompetent ones, microsporidiosis produces minimal clinically apparent disease. Despite their microscopic size, microsporidia are capable of causing systemic infection within a few days. However, the mechanisms by which microsporidia reach target tissues during acute infection remain unclear. Out of four genotypes of Encephalitozoon cuniculi, only three are available for experimental studies, with E. cuniculi genotype II being the best characterized. Methods: In the present study, we tested the association between inflammation induction in immunocompetent and immunodeficient mice and the presence of spores of E. cuniculi genotypes I and III in selected organs using molecular methods and compared the results with previously published data on E. cuniculi genotype II. Results: We reported the positive connection between inflammation induction and the significant increase of E. cuniculi genotypes I and III occurrence in inflammatory foci in both immunocompetent BALB/c and immunodeficient severe combined immunodeficient (SCID) mice in the acute phase of infection. The induction of inflammation resulted in increased concentration of E. cuniculi of both genotypes in the site of inflammation, as previously reported for E. cuniculi genotype II. Moreover, our study extended the spectrum of differences among E. cuniculi genotypes by the variations in dispersal rate within host bodies after experimentally induced inflammation. Conclusion: The results imply possible involvement of immune cells serving as vehicles transporting E. cuniculi towards inflammation foci. The elucidation of possible connection with pro-inflammatory immune responses represents an important challenge with implications for human health and the development of therapeutic strategies.
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Studies on the pathogenesis and immune responses of Cryptosporidium infection and development of drugs and vaccines use mostly immunocompromised mouse models. In this study, we establish an immunocompetent mouse model of cryptosporidiosis with high intensity and long duration of infection. METHODS: We have obtained a Cryptosporidium tyzzeri isolate from laboratory mice, and infect adult C57BL/6 J mice experimentally with the isolate for determinations of infectivity, infection patterns, pathological changes, and transcriptomic responses. RESULTS: The isolate has an ID50 of 5.2 oocysts, with oocyst shedding lasting at high levels for >2 months. The oocyst shedding is boosted by immunosuppression of animals and suppressed by paromomycin treatment. The isolate induces strong inflammatory and acquired immune responses, but down-regulates the expression of α-defensins in epithelium. Comparative genomics analysis has revealed significant sequence differences from other isolates in subtelomeric genes. The down-regulation of the expression of α-defensins may be responsible for the high-intensity and long-lasting infection in this animal model. CONCLUSIONS: The immunocompetent mouse model of cryptosporidiosis developed has the advantages of high oocyst shedding intensity and long oocyst shedding duration. It provides an effective mechanism for the propagation of Cryptosporidium, evaluations of potential therapeutics, and studies of pathogen biology and immune responses.
- MeSH
- alfa-defensiny * MeSH
- Cryptosporidium parvum * MeSH
- Cryptosporidium * fyziologie MeSH
- feces MeSH
- kryptosporidióza * patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- oocysty MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Objectives: Patients with inflammatory bowel disease (IBD) are susceptible to intestinal opportunistic infections due to both defective mucosal immunity and altered immune response resulting from immunosuppressive treatment. Microsporidia infecting the gastrointestinal tract and causing diarrhoea can potentially affect the course of IBD. Methods: Stool samples (90 IBD children and 121 healthy age-matched controls) were screened for Encephalitozoon spp. and Enterocytozoon bieneusi by microscopy and polymerase chain reaction followed by sequencing. Results:E. bieneusi genotype D was found in seven out of 90 (7.8%) IBD children. No children from the control group were infected, making the pathogen prevalence in the IBD group significant (P = 0.002). Furthermore, infection was confirmed only in patients receiving immunosuppressive treatment (P = 0.013). Conclusions: Children with IBD are at risk of intestinal E. bieneusi infection, especially when receiving immunosuppressive treatment. Therefore, microsporidia should be considered as a significant infectious agent in this group of patients.
- Publikační typ
- časopisecké články MeSH
Zoonotic pathogen transmission is considered a leading threat to the survival of non-human primates and public health in shared landscapes. Giardia spp., Cryptosporidium spp. and Microsporidia are unicellular parasites spread by the fecal-oral route by environmentally resistant stages and can infect humans, livestock, and wildlife including non-human primates. Using immunoassay diagnostic kits and amplification/sequencing of the region of the triosephosphate isomerase, small ribosomal subunit rRNA and the internal transcribed spacer genes, we investigated Giardia, Cryptosporidium, and microsporidia infections, respectively, among humans, domesticated animals (livestock, poultry, and dogs), and wild nonhuman primates (eastern chimpanzees and black and white colobus monkeys) in Bulindi, Uganda, an area of remarkably high human-animal contact and spatial overlap. We analyzed 137 fecal samples and revealed the presence of G. intestinalis assemblage B in two human isolates, G. intestinalis assemblage E in one cow isolate, and Encephalitozoon cuniculi genotype II in two humans and one goat isolate. None of the chimpanzee and colobus monkey samples were positive for any of the screened parasites. Regular distribution of antiparasitic treatment in both humans and domestic animals in Bulindi could have reduced the occurrence of the screened parasites and decreased potential circulation of these pathogens among host species.
- Publikační typ
- časopisecké články MeSH
Cryptosporidium spp. are common protozoan pathogens in mammals. With pet rodents being integrated into modern life, the potential roles of them in transmitting parasites to humans need assessments. In the present study, we examined the occurrence of Cryptosporidium spp. in pet rodents in Guangdong, south China. A total of 697 fecal samples were collected from 11 species of rodents in seven pet shops, one pet market and one farm. Cryptosporidium spp. were identified by PCR analysis of the small subunit rRNA gene. An overall infection rate of 36.9% (257/697) was obtained, with infection rates varying from 9.3% in chinchillas, 52.3% in guinea pigs, 57.1% in squirrels, to 68.4% in cricetid animals. Nine Cryptosporidium species and genotypes were identified, including C. wrairi (in 129 guinea pigs), C. andersoni (in 34 hamsters), C. homai (in 32 guinea pigs), Cryptosporidium hamster genotype (in 30 hamsters), C. ubiquitum (in 24 chinchillas and squirrels), C. parvum (in 2 chinchillas), Cryptosporidium ferret genotype (in 2 chipmunks), C. muris (in 1 hamster and 1 guinea pig), and Cryptosporidium chipmunk genotype V (in 1 chinchilla and 1 chipmunk). Sequence analysis of the 60 kDa glycoprotein gene identified three subtype families of C. ubiquitum, including family XIId in 15 chinchillas, XIIa in 5 chinchillas, and a new subtype family (XIIi) in 1 squirrel. The identification of C. parvum and C. ubiquitum in pet rodents suggests that these animals, especially chinchillas, could serve as reservoirs of human-pathogenic Cryptosporidium spp. Hygiene should be practiced in the rear and care of these animals, and One Health measures should be developed to reduce the occurrence of zoonotic Cryptosporidium infections due to contact with pet rodents.
- Publikační typ
- časopisecké články MeSH
Out of three genotypes of Encephalitozoon cuniculi (I-III) available for experimental studies, E. cuniculi genotype I remains the less characterized. This study describes for the first time individual phases of microsporidiosis caused by E. cuniculi genotype I and efficacy of albendazole treatment in immunocompetent BALB/c and C57Bl/6 mice and immunodeficient SCID, CD4-/- and CD8-/- mice using molecular detection and quantification methods. We demonstrate asymptomatic infection despite an intense dissemination of microsporidia into most organs within the first weeks post infection, followed by a chronic infection characterized by significant microsporidia persistence in immunocompetent, CD4-/- and CD8-/- mice and a lethal outcome for SCID mice. Albendazole application led to loss E. cuniculi genotype I infection in immunocompetent mouse strains, decreased spore burden by half in CD4-/- and CD8-/- mice, and prolongation of survival of SCID mice. These results showed Encephalitozoon cuniculi genotype I infection extend and albendazole sensitivity was comparable to E. cuniculi genotype II, but the infection onset speed and mortality rate was similar to E. cuniculi genotype III. These imply that differences in the course of infection and the response to treatment depend not only on immunological status of the host, but also on the genotype causing the infection.
- MeSH
- albendazol aplikace a dávkování MeSH
- antigeny CD4 genetika MeSH
- antigeny CD8 genetika MeSH
- antiinfekční látky aplikace a dávkování MeSH
- Encephalitozoon cuniculi klasifikace genetika MeSH
- encephalitozoonóza imunologie parazitologie MeSH
- genotyp MeSH
- imunokompetence MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši SCID MeSH
- myši MeSH
- polymerázová řetězová reakce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Parasites of the genus Cryptosporidium Tyzzer, 1910 are one of the most common protistan parasites of vertebrates. Faecal samples from 179 red foxes (Vulpes vulpes [Linnaeus]), 100 grey wolves (Canis lupus Linnaeus), 11 golden jackals (Canis aureus Linnaeus), and 63 brown bears (Ursus arctos Linnaeus) were collected in the Czech Republic, Poland and Slovakia. Samples were examined for the presence of Cryptosporidium spp. using microscopy and PCR/sequence analysis. Phylogenetic analysis based on the small subunit ribosomal RNA (SSU), actin and 60-kDa glycoprotein (gp60) genes using the maximum likelihood method revealed the presence of Cryptosporidium tyzzeri Ren, Zhao, Zhang, Ning, Jian et al., 2012 (n = 1) and C. andersoni Lindsay, Upton, Owens, Morgan, Mead et Blackburn, 2000 (n = 2) in red foxes, C. canis Fayer, Trout, Xiao, Morgan, Lai et Dubey, 2001 (n = 2) and C. ubiquitum Fayer, Santín et Macarisin, 2010 (n = 2) in grey wolves, and C. galli Pavlásek, 1999 in brown bears (n = 1) and red foxes (n = 1). Subtyping of isolates of C. ubiquitum and C. tyzzeri based on sequence analysis of gp60 showed that they belong to the XIId and IXa families, respectively. The presence of specific DNA of C. tyzzeri, C. andersoni and C. galli, which primarily infect the prey of carnivores, is probably the result of their passage through the gastrointestinal tract of the carnivores. Finding C. ubiquitum XIId in wolves may mean broadening the host spectrum of this subtype, but it remains possible this is the result of infected prey passing through the wolf - in this case deer, which is a common host of this parasite. The dog genotype of C. canis was reported for the first time in wolves.
- MeSH
- Carnivora parazitologie MeSH
- Cryptosporidium * genetika izolace a purifikace MeSH
- feces parazitologie MeSH
- fylogeneze MeSH
- genetická variace MeSH
- genotypizační techniky MeSH
- kryptosporidióza epidemiologie MeSH
- lišky parazitologie MeSH
- malé podjednotky ribozomu genetika MeSH
- medvědovití parazitologie MeSH
- prevalence MeSH
- protozoální DNA genetika MeSH
- protozoální geny MeSH
- psi parazitologie MeSH
- šakali parazitologie MeSH
- vlci parazitologie MeSH
- zvířata MeSH
- Check Tag
- psi parazitologie MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
- Polsko MeSH
- Slovenská republika MeSH
