Biology subjects

Spadacci-Morena, D. D.

Publications and source records attributed to Spadacci-Morena, D. D..

3 recordsLinked to original sources

bioRxiv2019

Can immunosuppressed mice control oral infection by the opportunistic pathogen Encephalitozoon intestinalis?

Intestinal mucosa (IM), or the outer surface of the intestine, serves at the primary site for the interaction of various pathogens that cause infection via the oral route. Thus, IM is crucial for developing an efficient adaptive immune response against pathogenic micro-organisms, thereby preventing their colonization and subsequent infection. In the present study, we investigated the immune response to Encephalitozoon intestinalis-caused infection in the IM and gut-associated lymphoid tissue (GALT) in C57BL/6 female mice. To mimic an immunosuppressive condition, the mice were treated with cyclophosphamide (Cy). Histopathology revealed lymphoplasmacytic enteritis at 7 and 14 days-post-infection (dpi) in all infected groups; however, inflammation diminished at 21 and 28 dpi. Cy treatment also led to a higher number of E. intestinalis spores and lesions, which reduced at 28 dpi. In addition, flow cytometry analysis demonstrated CD4+ and CD8+ T cells to be predominant immune cells, with a significant increase in both Th1 and Th2 cytokines at 7 and 14 dpi, as demonstrated by histopathology. In conclusion, Cy treatment reduced GALT (Peyers plaques and mesenteric lymph nodes) and peritoneum populations but increased the T-cell population in the intestinal mucosa and the production of pro-inflammatory cytokines, which were able to eliminate this opportunistic fungus and reduced the infection.

pathology↗

bioRxiv2019

B-1 cell-mediated modulation of M1-macrophage profile can ameliorate microbicidal functions and disrupt the evasion mechanisms of Encephalitozoon cuniculi

Here, we have investigated the possible effect of B-1 cells on the activity of peritoneal macrophages in E. cuniculi infection. In the presence of B-1 cells, peritoneal macrophages had an M1 profile with showed increased phagocytic capacity and index, associated with the intense microbicidal activity, increased proinflammatory cytokines production and a higher percentage of apoptotic death. The absence of B-1 cells was associated with a predominance of the M2 macrophages, indicating reduced phagocytic capacity and index, microbicidal activity, proinflammatory cytokine production, and apoptotic death, but equal death rate. In addition, in the M2 macrophages, spores of phagocytic E. cuniculi with polar tubular extrusion were observed, which is an important mechanism of evasion of the immune response. The results showed the importance of B-1 cells in the modulation of macrophage function against E. cuniculi infection, increasing microbicidal activity, and reducing the fungal mechanisms involved in the evasion of the immune response.\n\nHighlightsO_LIE. cuniculi phagocytosis and microbicidal activity by macrophages increases in the presence of B-1 cells\nC_LIO_LIM1 macrophage profiles were predominant in the presence of B-1 cells\nC_LIO_LIExtrusion of the polar tubule of E. cuniculi occur inside M2 macrophages in cultures without B-1 cells\nC_LIO_LIB-1 cells derived phagocytes (B-1CDP) identified with microbicidal activity against spores of E. cuniculi\nC_LI\n\nAuthor SummaryThe adaptive immune response plays a key role against Encephalitozoon cuniculi, an opportunistic fungus for T cells immunodeficient patients. The role of B cells and antibody play in natural resistance to Encephalitozoon cuniculi remains unresolved. Previously, we demonstrated that B-1 deficient mice (XID), an important component of innate immunity, were more susceptible to encephalitozoonosis, despite the increase in the number of CD4+ and CD8+ T lymphocytes. Here we observed that the absence of B-1 cells was associated with a larger population of M2 macrophages, an anti-inflammatory profile, which had lower microbicidal activity and phagocytic E. cuniculi spores were seen with the extrusion of the polar tubule, which is an important mechanism of evasion of the immune response. The results showed the importance of B-1 cells in the modulation of macrophage function against E. cuniculi infection, increasing microbicidal activity, and reducing the fungal mechanisms involved in the evasion of the immune response.

microbiology↗

bioRxiv2018

Cyclophosphamide immunosuppressed Xid mice model clarify the protective role of B cells in experimental encephalitozoonosis

Encephalitozoon cuniculi is an intracellular pathogen that stablishes a balanced relationship with immunocompetent individuals, which is dependent of T lymphocytes activity. We previously showed X-linked immunodeficiency (XID - B cell deficient) mice are more susceptible to encephalitozoonosis and B-1 cells presence influences in the immune response. Because XID mice are deficient both in B-1 and B-2 cells, here we investigate the role of these cells against E. cuniculi infection using cyclophosphamide (Cy) immunosuppressed murine model to exacerbate the infection. XID mice presented lethargy and severe symptoms, associated with encephalitozoonosis and there was an increase in the peritoneal populations of CD8+ and CD4+ T lymphocytes and macrophages and also in the proinflammatory cytokines IFN-{gamma}, TNF- and IL-6. In BALB/c mice, no clinical signs were observed and there was an increase of T lymphocytes and macrophages in the spleen, showing an effective immune response. B-2 cells transfer to XID mice resulted in reduction of symptoms and lesion area with increase of B-2 and CD4+ T populations in the spleen. B-1 cells transfer increased the peritoneal populations of B-2 cells and macrophages and also reduced the symptoms. Therefore, the immunodeficiency of B cells associated to Cy immunosuppression condition leads to disseminated and severe encephalitozoonosis in XID mice with absence of splenic immune response and ineffective local immune response, evidencing the B-1 and B-2 cells role against microsporidiosis.\n\nAuthor summaryThe adaptive immune response plays a key role against Encephalitozoon cuniculi, an opportunistic fungus for T cells immunodeficient patients. The role of B cells and antibody play in natural resistance to Encephalitozoon cuniculi remains unresolved. Previously, we demonstrated that B-1 deficient mice (XID), an important component of innate immunity, were more susceptible to encephalitozoonosis, despite the increase in the number of CD4+ and CD8+ T lymphocytes. In order to better understand the role of B-1 and B-2 cells and the relationship with the other cells of the immune response in encephalitozoonosis, we infected with E. cuniculi in cyclophosphamide immunosuppressed mice. Here we demonstrate that infected XID mice showed reduction of T cells and macrophages and increase of proinflammatory cytokines associated with disseminated and severe encephalitozoonosis with presence of abdominal effusion and lesions in multiple organs. This pattern of infection observed in mice with genetic deficiency in T cells, so we suggest that the absence of B-1 cells affects the cytotoxic capacity of these lymphocytes. When we transfer B-2 cells to XID mice, the lesion areas caused by the fungus, the populations of T lymphocytes in the peritoneum and the proinflammatory cytokines decrease, indicating a better resolution of the infection. We speculate that B-1 and B-2 cells participate in the immune response against E. cuniculi, interacting with the other components effective in immunity. The results shown here indicate that B-1 cells as a constituent of the innate response to microsporidia.

pathology↗