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
Background: Microsporidia of the genus Encephalitozoon are generally connected with severe infections with lethal outcome in immunodeficient hosts. In immunocompetent hosts, microsporidiosis typically establishes a balanced host-parasite relationship that produces minimal clinically overt disease. Although the alimentary tract represents one of the main primary target tissues, the mechanisms of reaching other tissues during systemic microsporidian infections remain unclear. Methods: In the present study, we tested the relation between inflammation induction in immunocompetent and immunodeficient mice and the presence of spores of E. cuniculi genotype II in selected organs and in fecal specimens by using molecular and histology methods. Results: We reported the positive connection between inflammation induction and the significant increase of E. cuniculi genotype II occurrence in inflammation foci in both immunocompetent BALB/c and immunodeficient severe combined immunodeficient (SCID) mice in the acute phase of infection and the re-activation of latent microsporidial infection following inflammation induction in immunocompetent mice. Conclusion: The results imply possible involvement of immune cells serving as vehicles transporting E. cuniculi genotype II purposefully across the whole host body towards inflammation. With increasing number of records of infections, it is necessary to reconsider microsporidia as agents responsible for various pathologies. The elucidation of possible connection with pro-inflammatory immune responses represents an important challenge with consequences for human health and development of therapeutic strategies.
- Publikační typ
- časopisecké články MeSH
Encephalitozoon cuniculi genotype III disseminated intensively into most of the organs in all strains of mice, followed by a chronic infection with massive microsporidia persistence in immunodeficient mice and a partial decrease in C57Bl/6 mice. Treatment with 0.2 mg Albendazole/mouse/day temporarily reduces the number of affected organs in immunocompetent C57Bl/6 mice, but not in CD4-/- and CD8-/- mice. The application of medication temporarily decreased the spore burden at least by one order of magnitude in all groups. These results demonstrate that the E. cuniculi genotype III infection had a progressive course and surprisingly, Albendazole treatment had only a minimal effect. The E. cuniculi genotype III spore burden in individual organs reached up to 108 or 109 in immunocompetent or immunodeficient mice, respectively; however, these mice did not demonstrate any obvious clinical signs of microsporidiosis, and the immunodeficient mice survived longer. Our findings clearly show that the survival of mice does not correspond to spore burden, which provides new insight into latent microsporidiosis from an epidemiological point of view.
- MeSH
- albendazol terapeutické užití MeSH
- antigeny CD4 genetika MeSH
- antigeny CD8 genetika MeSH
- Cercopithecus aethiops MeSH
- Encephalitozoon cuniculi genetika MeSH
- encephalitozoonóza farmakoterapie mikrobiologie patologie MeSH
- genotyp * MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Of four genotypes of Encephalitozoon cuniculi, E. cuniculi genotype II is considered to represent a parasite that occurs in many host species in a latent asymptomatic form, whereas E. cuniculi genotype III seems to be more aggressive, and infections caused by this strain can lead to the death of even immunocompetent hosts. Although albendazole has been considered suitable for treatment of Encephalitozoon species, its failure in control of E. cuniculi genotype III infection has been reported. This study determined the effect of a 100× recommended daily dose of albendazole on an Encephalitozoon cuniculi genotype III course of infection in immunocompetent and immunodeficient mice and compared the results with those from experiments performed with a lower dose of albendazole and E. cuniculi genotype II. The administration of the regular dose of abendazole during the acute phase of infection reduced the number of affected organs in all strains of mice and absolute counts of spores in screened organs. However, the effect on genotype III was minor. Surprisingly, no substantial effect was recorded after the use of a 100× dose of albendazole, with larger reductions seen only in the number of affected organs and absolute counts of spores in all strains of mice, implying variations in albendazole resistance between these Encephalitozoon cuniculi genotypes. These results imply that differences in the course of infection and the response to treatment depend not only on the immunological status of the host but also on the genotype causing the infection. Understanding how microsporidia survive in hosts despite targeted antimicrosporidial treatment could significantly contribute to research related to human health.
- MeSH
- albendazol aplikace a dávkování farmakologie MeSH
- antifungální látky aplikace a dávkování farmakologie MeSH
- antigeny CD4 genetika MeSH
- antigeny CD8 genetika MeSH
- buněčné linie MeSH
- Cercopithecus aethiops MeSH
- Encephalitozoon cuniculi účinky léků genetika izolace a purifikace MeSH
- encephalitozoonóza farmakoterapie MeSH
- genotyp MeSH
- hostitel s imunodeficiencí imunologie MeSH
- mikrobiální testy citlivosti MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši SCID MeSH
- myši MeSH
- počet mikrobiálních kolonií MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study describes the prevalence and concentration of Encephalitozoon cuniculi spores in pork meat and evaluates the effect of sausage fermentation on E. cuniculi infectivity for immunodeficient (severe combined immunodeficient) and immunocompetent (BALB/c and C57BL/6) mice. Using a nested polymerase chain reaction (PCR) approach, E. cuniculi genotype II was detected in the meat from 2 out of 50 pig carcasses at slaughter facilities, with 60-250 spores per gram detected by quantitative PCR. Under experimental conditions, 3000 E. cuniculi genotype II spores per gram of meat remained infective for mice following fermentation at 24°C for 48 h. Based on these findings, fermented meat products should be considered as a potential source of E. cuniculi infection in humans.
- MeSH
- Encephalitozoon cuniculi izolace a purifikace patogenita MeSH
- encephalitozoonóza mikrobiologie MeSH
- fermentované potraviny mikrobiologie MeSH
- hostitel s imunodeficiencí MeSH
- maso mikrobiologie MeSH
- modely u zvířat MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- potravinářská mikrobiologie * MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH