Encephalitozoon cuniculi takes advantage of efferocytosis to evade the immune response.
Authors: Dalboni Luciane Costa, Alvares Saraiva Anuska Marcelino, Konno Fabiana Toshie de Camargo, Perez Elizabeth Cristina, Codeceira Jéssica Feliciana, Spadacci-Morena Diva Denelle, Lallo Maria Anete
Journal: PloS one
Summary
# Editorial Summary: Encephalitozoon cuniculi and Immune Evasion Encephalitozoon cuniculi, a microsporidian pathogen of particular concern in immunocompromised horses and rabbits, exploits a normally protective immune mechanism—the clearance of dead cells by macrophages—to establish infection and evade CD8+ T cell responses. Researchers cultured bone marrow-derived macrophages from mice and exposed them to apoptotic cells (infected or uninfected) before challenging them with E. cuniculi spores, measuring spore internalisation, macrophage surface markers, cytokine production, and ultrastructural pathogen development. Macrophages that had engulfed apoptotic material showed significantly higher spore uptake and evidence of parasite multiplication within the cells; critically, efferocytosis of infected apoptotic bodies allowed the pathogen to proliferate intracellularly, whilst macrophages shifted toward an M2 (anti-inflammatory) phenotype characterised by elevated CD206 expression and substantial IL-10 and IL-6 release. This explains why macrophages may function as "Trojan horses," inadvertently sheltering the microsporidia rather than eliminating it—a mechanism with implications for understanding chronic or recurrent microsporidiosis in clinical equine and rabbit cases, particularly where secondary infections or tissue damage drive macrophage-mediated efferocytosis.
Read the full abstract on PubMed
Practical Takeaways
- •This study explains at a cellular level why E. cuniculi infections are difficult to clear, particularly in immunocompromised individuals; understanding this mechanism may inform future treatment strategies targeting macrophage polarization
- •The finding that macrophages facilitate pathogen survival rather than elimination highlights the importance of supporting adaptive immune responses (CD8+ T cells) rather than relying solely on innate immunity in microsporidiosis management
- •While this research is in vitro using mouse cells, it provides mechanistic insight into why E. cuniculi is an opportunistic pathogen and may guide development of immunomodulatory therapies to prevent macrophage polarization toward the M2 phenotype
Key Findings
- •Macrophages pre-incubated with apoptotic cells showed higher phagocytosis rates and internalized more E. cuniculi spores
- •E. cuniculi multiplication occurred inside macrophages, particularly after efferocytosis of infected apoptotic bodies
- •Efferocytosis triggered polarization of macrophages to M2 phenotype, characterized by high CD206 expression and IL-10/IL-6 release
- •Macrophages act as 'Trojan horses' by facilitating pathogen survival and immune evasion through the efferocytosis mechanism