Comparison of the Concentration of Encephalitozoon cuniculi Genotypes I and III in Inflammatory Foci Under Experimental Conditions

Abstract

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.

A mouse ear skin model to study the dynamics of innate immune responses against the microsporidian Encephalitozoon cuniculi

“…This method was not used because it could alter the spores and thus decrease their infectivity. We inoculated a high number of spores (10 7 ) into the ear tissue of LysM-EGFP transgenic mice, as in previously published rodent models (Sak and Ditrich, 2005;Kotková et al, 2017;Brdícková et al, 2020;Sak et al, 2021Sak et al, , 2022. Once set up, our protocol enabled us to analyze qualitatively and quantitatively, simultaneously the innate immune responses induced by E. cuniculi CW + fluorescent spores in mice and the fate of parasites at the tissue level.…”

“…At early time-points, bright fluorescent phagocytes, probably PMN, as they are the first cells to be recruited in an inflammatory context ( Filep, 2022 ), crossed the inoculation zone, or slowed down to remain in contact with spores for a very short time before leaving the injection area. These “quick” PMN could leave the injection site in response to chemokine signals and thus participate to parasite dissemination ( Nassonova et al, 2001 ; Sak et al, 2022 ). Among chemokines that play a role in PMN chemotaxis and activation during microsporidian infection, CXCL5 gene expression is strongly induced in a rodent model ( Fischer et al, 2007 ), but CXCL1 and CXCL8 could also play a key role.…”

Molecular Detection of Microsporidia in Rabbits (Oryctolagus cuniculus) in Tenerife, Canary Islands, Spain

“…Four genotypes based on the number of 5′-GTTT-3′ repeats in the internal transcribed spacer (ITS) of the rRNA have been described in E. cuniculi : genotype I (three repeats), genotype II (two repeats), genotype III (four repeats), and genotype IV (five repeats) [ 23 ]. Genotypes I, II, and III have been found in several bird species, rodents, carnivores, artiodactyls, non-human primates, and humans worldwide [ 24 , 25 ], while genotype IV has been detected in cats, dogs, marmots, and immunosuppressed humans [ 26 ]. In rabbits specifically, genotype I is the most frequent genotype [ 27 ] found, while genotype II has been reported in domestic rabbits from Slovakia [ 28 ] and China [ 17 ], and genotype III only in domestic rabbits from Slovakia [ 28 ].…”

Microsporidia (Encephalitozoon cuniculi) in Patients with Degenerative Hip and Knee Disease, Czech Republic

“…However, the unique mechanism of host cell invasion involving a highly specialized structure, the 10–50 μm long polar filament, enables only limited spread over short distances within the host. Therefore, the dissemination rate suggests the possible engagement of macrophages or other immune cells involved in inflammatory responses, which can serve as vehicles transporting microsporidia to foci outside of the intestine ( 9 , 10 ). Microsporidia are often overlooked in clinical samples because of problematic diagnoses, increasing the likelihood of hidden infections that can cause extensive tissue damage and various nonspecific pathologies and that often go without effective treatment ( 11 ).…”

“…E. cuniculi is considered a cause of osteolysis in hip periprosthetic tissue ( 17 ), and connections between proinflammatory immune responses and concentration of E. cuniculi in inflammatory foci have been reported ( 9 , 10 ). Understanding the risks for microsporidiosis within periprosthetic joints is essential for proper arthroplasty management.…”