Latent Microsporidiosis Caused by Encephalitozoon cuniculi in Immunocompetent Hosts: A Murine Model Demonstrating the Ineffectiveness of the Immune System and Treatment with Albendazole

Abstract

BackgroundMicrosporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression.AimsTo evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods.MethodsMice were per orally infected with 107 spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host’s organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis.ResultsWhereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment.ConclusionOur results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings stress the danger of latent microsporidiosis as a life-threatening risk factor especially for individuals undergoing chemotherapy and in transplant recipients of organs originating from infected donors.

Concurrent Infection of the Urinary Tract with Encephalitozoon cuniculi and Enterocytozoon bieneusi in a Renal Transplant Recipient

“…A similar effect was reported in cases of HIV-infected patients, who cleared the microsporidiosis after immune reconstitution in the absence of specific antiparasitic treatment (16). The same results were obtained experimentally using murine model hosts (9). Taking into account that only partially effective chemotherapy against Encephalitozoon spp.…”

“…However, since organ donors are not routinely tested for microsporidial infection, the organ transplant recipient could become infected via a microsporidium-positive graft. Furthermore, due to decreased recipient immunity, microsporidia could reactivate (9). The infection could also be responsible for decreased function of graft or cause pathologies without an identified causative agent, such as in the patient in our study.…”

“…In immunocompromised individuals, chronic diarrhea may lead to malabsorption and wasting (6,8). While E. bieneusi infection is considered to occur mainly in the gastrointestinal tract and biliary tree, species of the genus Encephalitozoon have been shown to disseminate, causing central nervous system, ocular, respiratory, and urinary tract infections (5,6,8,9). Because of various susceptibilities of these pathogens for drugs, infections caused by Encephalitozoon spp.…”

Microsporidia–host interactions

“…For example, fumagillin is one of the few compounds that are effective in killing some species of microsporidia but unfortunately it is toxic to humans [5]. Some groups report that the prevalence of microsporidia infections in humans increasing, with many individuals carrying latent and asymptomatic infections [6-8]. For further details on the clinical relevance of microsporidia, we refer readers to a recent review of this topic [9].…”

Interleukin-12-Producing CD103+CD11b−CD8+Dendritic Cells Are Responsible for Eliciting Gut Intraepithelial Lymphocyte Response against Encephalitozoon cuniculi

“…Lately, it has been reported that microsporidial infections can cause complications in non-HIV populations, especially those receiving organ transplants (6)(7)(8)(9). In a very recent study, Kotkova et al demonstrated that microsporidiosis was probably a latent infection, which could reactivate in an immunocompromised situation, further highlighting the importance of studying the immune response against this ubiquitous pathogen (10). An experimental murine model using E. cuniculi mimics the human infection and has commonly been used to investigate the host immune response (11).…”