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Encephalitozoon intestinalis: humoral responses in interferon-gamma receptor knockout mice infected with a
Y El Fakhry1, A Achbarou, I Desportes-Livage
1INSERM U313, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Paris, France.
Abstract:
IFN-gamma receptor knockout mice and wild-type mice were infected per os with Encephalitozoon intestinalis. Both groups developed an infection that was chronic in the mutant mice whereas it was only transient in wild-type mice. The infection of mutant mice was characterized by the continual shedding of spores in feces, splenomegaly, the enlargement of the biliary tract, and the occurrence of numerous nodules in the liver and in the small intestine wall. The humoral response was studied by ELISA, IFA, and Western blotting. ELISA titers of anti-E. intestinalis antibodies of IgG, IgM, and IgA isotypes were higher in IFN-gamma R0/0 mice than in wild-type mice and they increased in time after infection. Levels of IgG2a were inferior to those of IgG1 in mutant mice in contrast to wild-type mice. High levels of parasite specific antibodies were accompanied by an increase in type 2 cytokines (IL-4 and IL-10) secretion in the duodenum of IFN-gamma R0/0 mice. The E. intestinalis spore wall was recognized by IgM, IgG, and IgA from all infected mice whereas the extruded polar tube only reacted with IgG and IgA from IFN-gamma R0/0 mice after 45 days of the infection. IFN-gamma R0/0 mice IgG and IgA reacting with polar tube identified also a series of proteins which could be components of this structure. On the proteins recognized by all infected mice sera, two were first recognized by IgM at day 15 and then by IgG at day 30 in wild-type (WT) mice. The persistent reactivity of all proteins in mutant mice is consistent with the chronicity of the infection in these animals; in contrast, their resorption at day 30 in WT animals corroborates the transient character of the infection in these mice. The correlation between the evolution of the proteic pattern and the development of the infection provides evidence of the validity of this murine model to study human microsporidiosis. Indeed the reported results confirm the potential value of serological methods for diagnosing E. intestinalis infection in immunocompetent and in immunocompromised human subjects, for elucidating the age pattern of the microsporidiosis and also for identifying risk groups.
Insights
IFN-gamma receptor knockout mice show chronic Encephalitozoon intestinalis infections, unlike wild-type mice. This study highlights the potential of serological methods for diagnosing human microsporidiosis.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Microsporidiosis, caused by Encephalitozoon intestinalis, can lead to chronic infections, particularly in immunocompromised individuals.
- The role of the interferon-gamma (IFN-gamma) receptor in controlling E. intestinalis infections is not fully understood.
Purpose of the Study:
- To investigate the impact of IFN-gamma receptor deficiency on the course and immune response to E. intestinalis infection.
- To evaluate the utility of serological methods for diagnosing microsporidiosis.
Main Methods:
- Infection of IFN-gamma receptor knockout (IFN-gamma R0/0) and wild-type (WT) mice with E. intestinalis.
- Assessment of infection chronicity, clinical signs, and host immune responses (humoral and cytokine).
- Serological analysis using ELISA, IFA, and Western blotting to detect anti-E. intestinalis antibodies and identify target antigens.
Main Results:
- IFN-gamma R0/0 mice developed chronic infections with persistent spore shedding and pathological changes, while WT mice had transient infections.
- Higher antibody titers (IgG, IgM, IgA) and a shift towards IgG1 over IgG2a were observed in IFN-gamma R0/0 mice.
- Increased type 2 cytokines (IL-4, IL-10) were detected in the duodenum of IFN-gamma R0/0 mice.
- Antibody reactivity to parasite antigens, particularly the polar tube, differed between knockout and WT mice, correlating with infection chronicity.
Conclusions:
- IFN-gamma signaling is crucial for controlling E. intestinalis infections.
- The murine model effectively mimics human microsporidiosis, validating its use for studying the disease.
- Serological diagnostics hold promise for detecting E. intestinalis infections in diverse human populations and identifying at-risk individuals.