Immunohistochemical localization of TNF-α and IL-4 in granulomas of immunocompetent and immunosuppressed New Zealand white rabbits infected with Encephalitozoon cuniculi

C Dávila-Martínez; U Castillo-Velázquez; A Soto-Domínguez; A M Nevárez-Garza; A Y Arce-Mendoza; G Hernandez-Vidal; D E Zamora-Avila; L E Rodriguez-Tovar

doi:10.1016/j.cyto.2020.155055

Immunohistochemical localization of TNF-α and IL-4 in granulomas of immunocompetent and immunosuppressed New Zealand white rabbits infected with Encephalitozoon cuniculi

Cytokine. 2020 Mar 14:130:155055. doi: 10.1016/j.cyto.2020.155055. Online ahead of print.

Authors

C Dávila-Martínez¹, U Castillo-Velázquez¹, A Soto-Domínguez², A M Nevárez-Garza¹, A Y Arce-Mendoza³, G Hernandez-Vidal⁴, D E Zamora-Avila⁵, L E Rodriguez-Tovar⁶

Affiliations

¹ Cuerpo Académico de Zoonosis y Enfermedades Emergentes, Facultad de Medicina Veterinaria y Zootecnia, UANL, General Escobedo, N. L. C.P. 66050, Mexico.
² Departamento de Histología, Facultad de Medicina, UANL, Monterrey, N. L. C.P. 64460, Mexico.
³ Cuerpo Académico de Inmunología Clínica y Dermatología, Facultad de Medicina, UANL, Col. Mitras Centro, Monterrey, N. L. C.P. 64460, Mexico.
⁴ Cuerpo Académico de Patobiología, Facultad de Medicina Veterinaria y Zootecnia, UANL, General Escobedo, N. L. C.P. 66050, Mexico.
⁵ Cuerpo Académico de Epidemiologia Veterinaria, Facultad de Medicina Veterinaria y Zootecnia, UANL, General Escobedo, N. L. C.P. 66050, Mexico.
⁶ Cuerpo Académico de Zoonosis y Enfermedades Emergentes, Facultad de Medicina Veterinaria y Zootecnia, UANL, General Escobedo, N. L. C.P. 66050, Mexico. Electronic address: luis.rodrigueztv@uanl.edu.mx.

PMID: 32182455
DOI: 10.1016/j.cyto.2020.155055

Abstract

Encephalitozoon cuniculi is a fungi-related, obligate, zoonotic, spore-forming intracellular eukaryotic microorganism. This emerging pathogen causes granulomas to form in the brain and kidneys of infected individuals. The objective of the current study was to detect the distribution of TNF-α- and IL-4-positive cells using immunohistochemistry within these granulomas in both infected immunocompetent (group A) and immunosuppressed (group B) New Zealand white rabbits. In the brain, labeled TNF-α immune cells were mainly located in the granuloma peripheries in group B. Granulomas examined in the kidneys of groups A and B were TNF-α positive, but were significantly different (p < 0.001) when compared with the brain. IL-4-producing immune cells in the brain and kidneys were disseminated within granulomas in groups A and B; however, no significant difference (p > 0.05), was observed. IL-4 positive cells were more numerous in brain sections of group B and differed significantly (p < 0.05) when compared with kidneys. Granulomas were not observed in control animals (groups C and D). In conclusion, we identified TNF-α positive cells in both the brain and kidneys of immunocompetent and immunosuppressed animals; IL-4 positive cells were numerous in the brains of immunosuppressed rabbits; however, in terms of percentage were numerous in the brains of immunocompetent rabbits. Immunosuppression appeared to stimulate a change in the cellular phenotype of Th1- to Th2-like granulomas in the brain and kidneys via an unknown mechanism. Expression of pro- and pre-inflammatory cytokines in microsporidian granulomas suggests a mechanism by which E. cuniculi evades the immune response, causing more severe disease. These results increase our understanding of TNF-α and IL-4-positive cells within the E. cuniculi granuloma microenvironment.

Keywords: Encephalitozoon cuniculi; Granuloma; Immunohistochemistry; Interleukin-4; Rabbit; Tumor necrosis factor-α.