Mice with genetic and induced B-cell deficiency as a model for disseminated encephalitozoonosis

Author(s)

Moyses, Carla Renata Serantoni ; Alvares-Saraiva, Anuska Marcelino ; Perez, Elizabeth Cristina ; Spadacci-Morena, Diva Denelle ; da Costa, Lidiana Flora Vidoto ; Xavier, Jose Guilherme ; Lallo, Maria Anete

• Document type: Journal article
• Source: COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES; v. 81, p. 9-pg., 2022-02-01.

Abstract

Encephalitozoon cuniculi, an intracellular pathogen, lives in a balanced relationship with immunocompetent individuals based on the activity of T lymphocytes. We previously highlighted the greater susceptibility of B-1 celldeficient mice (XID mice) to encephalitozoonosis. This study aimed to develop a model of disseminated and severe encephalitozoonosis in mice with combined immunodeficiency to elucidate the role of B cells. To address this objective, cyclophosphamide (Cy)-treated BALB/c and XID mice were inoculated with E. cuniculi, followed by the evaluation of the immune response and histopathological lesions. Immunosuppressed BALB/c mice manifested no clinical signs with an increase in the populations of T lymphocytes and macrophages in the spleen. Immunosuppressed and infected XID mice revealed elevated T cells, macrophages populations, and proinflammatory cytokines levels (IFN-gamma, TNF-alpha, and IL-6) with the presence of abdominal effusion and lesions in multiple organs. These clinical characteristics are associated with extensive and severe encephalitozoonosis. The symptoms and lesion size were reduced, whereas B-2 and CD4+ T cells populations were increased in the spleen by transferring B-2 cells adoptive to XID mice. Moreover, B-1 cells adoptive transfer upregulated the peritoneal populations of B-2 cells and macrophages but not T lymphocytes and decreased the symptoms. Herein, we speculated the consistency in the development of severe and disseminated encephalitozoonosis in mice with genetic deficiency of Bruton's tyrosine kinase (Btk) associated with Cy immunosuppression develop with that of the models with T cell deficiency. Taken together, these data emphasized the crucial role of B cells in the protective immune response against encephalitozoonosis. (AU)

• FAPESP's process: 15/25948-2 - Murine microsporidiosis - the role of M1 and M2 macrophages, phagocytes derived from B-1 cells and efferocytossis
• Grantee: Maria Anete Lallo
• Support Opportunities: Regular Research Grants