B‐1 cells produce insulin and abrogate experimental streptozotocin‐induced diabetes

Alvares-Saraiva, Anuska Marcelino; Novo, Marilia Campos Tavares; Oliveira, Vivian Cristina de; Maricato, Juliana Terzi; Lopes, José Daniel; Popi, Ana Flávia; Mariano, Mário

doi:10.1002/eji.201445409

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…Phenotypical cell analysis included the quantification of macrophages, B and T lymphocytes. Pre-B-1 CDP is a stage of differentiation of B-1 in B-1 CDP, which is described in infection and also diabetes mice model [ 20 , 21 ]. There was a significant decrease of peritoneal B-1, B-2 and CD4 + T lymphocytes of DM and DM-Infected mice than non-diabetic ( Infected and Uninfected ) mice ( Fig 3 ), showing that DM condition decreased the immune response.…”

Section: Resultsmentioning

confidence: 99%

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Diabetes mellitus increases the susceptibility to encephalitozoonosis in mice

et al. 2017

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Microsporidiosis are diseases caused by opportunistic intracellular fungi in immunosuppressed individuals, as well as in transplanted patients, the elderly and children, among others. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and decreased T cell response, neutrophil function, humoral immunity failure, increasing the susceptibility to infections. Here, we investigated the susceptibility of streptozotocin (STZ)-induced type I diabetic and/or immunosuppressed mice to encephalitozoonosis by Encephalitozoon cuniculi. Microscopically, granulomatous hepatitis, interstitial pneumonia and pielonephritis were observed in all infected groups. STZ treatment induced an immunossupressor effect in the populations of B (B-1 and B2) and CD4+ T lymphocytes. Moreover, infection decreased CD4+ and CD8+ T lymphocytes and macrophages of DM mice. Furthermore, infection induced a significant increase of IL-6 and TNF-α cytokine serum levels in DM mice. IFN-γ, the most important cytokine for the resolution of encephalitozoonosis, increased only in infected mice. In addition to the decreased immune response, DM mice were more susceptible to encephalitozoonosis, associated with increased fungal burden, and symptoms. Additionally, cyclophosphamide immunosuppression in DM mice further increased the susceptibility to encephalitozoonosis. Thus, microsporidiosis should be considered in the differential diagnosis of comorbidities in diabetics.

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Section: Resultsmentioning

confidence: 99%

“…Type 1 DM was induced by intra-peritoneal administration of STZ at 50 mg/kg/day, during 5 consecutive days [ 20 , 21 ]. Ten days after the end of the treatment, 10 μl of blood was collected from the tail of each DM animal.…”

Section: Methodsmentioning

confidence: 99%

Diabetes mellitus increases the susceptibility to encephalitozoonosis in mice

et al. 2017

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“…Non-adherent cells were discarded and RPMI-1640 supplemented with 10% FCS (R10) was added to the adherent fraction. To obtain B-1 CDP, APerC from BALB/c mice were cultured and the enriched B-1 cells in the floating medium were collected from the third day [57]. Cultures of 0.5 × 10 6 cells/well were re-suspended in R10 and re-cultured under the same conditions as described above.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2019

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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 and a higher percentage of apoptotic death. The absence of B-1 cells was associated with a predominance of the M2 macrophages, reduced phagocytic capacity and index and microbicidal activity, increased pro-inflammatory and anti-inflammatory cytokines production, and higher percentual of necrosis death. In addition, in the M2 macrophages, spore of phagocytic E. cuniculi with polar tubular extrusion was 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.

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“…XID mice were adoptively transferred with B-2 cells from the spleen of BALB/c mice [46]. After tissue dissociation, lysis of red blood cells and centrifugation, a pellet was incubated with anti-CD16/32 for blocking Fc receptors, for 15 minutes at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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

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et al. 2018

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21Encephalitozoon cuniculi is an intracellular pathogen that stablishes a balanced relationship 22 with immunocompetent individuals, which is dependent of T lymphocytes activity. We 23 previously showed X-linked immunodeficiency (XID -B cell deficient) mice are more 24 susceptible to encephalitozoonosis and B-1 cells presence influences in the immune response. 25 Because XID mice are deficient both in B-1 and B-2 cells, here we investigate the role of these 26 cells against E. cuniculi infection using cyclophosphamide (Cy) immunosuppressed murine 27 model to exacerbate the infection. XID mice presented lethargy and severe symptoms, 28 associated with encephalitozoonosis and there was an increase in the peritoneal populations of 29 CD8 + and CD4 + T lymphocytes and macrophages and also in the proinflammatory cytokines 30 IFN-γ, TNF-α and IL-6. In BALB/c mice, no clinical signs were observed and there was an 31 increase of T lymphocytes and macrophages in the spleen, showing an effective immune 32 response. B-2 cells transfer to XID mice resulted in reduction of symptoms and lesion area with 33 increase of B-2 and CD4 + T populations in the spleen. B-1 cells transfer increased the peritoneal 34 populations of B-2 cells and macrophages and also reduced the symptoms. Therefore, the 35 immunodeficiency of B cells associated to Cy immunosuppression condition leads to 36 disseminated and severe encephalitozoonosis in XID mice with absence of splenic immune 37 response and ineffective local immune response, evidencing the B-1 and B-2 cells role against 38 microsporidiosis.39 40 lymphocytes 42 43 3 44 Author summary 45 46 The adaptive immune response plays a key role against Encephalitozoon cuniculi, an 47 opportunistic fungus for T cells immunodeficient patients. The role of B cells and antibody play 48 in natural resistance to Encephalitozoon cuniculi remains unresolved. Previously, we 49 demonstrated that B-1 deficient mice (XID), an important component of innate immunity, were 50 more susceptible to encephalitozoonosis, despite the increase in the number of CD4 + and CD8 + 51 T lymphocytes. In order to better understand the role of B-1 and B-2 cells and the relationship 52 with the other cells of the immune response in encephalitozoonosis, we infected with E. cuniculi 53 in cyclophosphamide immunosuppressed mice. Here we demonstrate that infected XID mice 54 showed reduction of T cells and macrophages and increase of proinflammatory cytokines 55 associated with disseminated and severe encephalitozoonosis with presence of abdominal 56 effusion and lesions in multiple organs. This pattern of infection observed in mice with genetic 57 deficiency in T cells, so we suggest that the absence of B-1 cells affects the cytotoxic capacity 58 of these lymphocytes. When we transfer B-2 cells to XID mice, the lesion areas caused by the 59 fungus, the populations of T lymphocytes in the peritoneum and the proinflammatory cytokines 60 decrease, indicating a better resolution of the infection. We speculate that B-1 and B-2 cells...

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B‐1 cells produce insulin and abrogate experimental streptozotocin‐induced diabetes

Cited by 7 publications

References 33 publications

Diabetes mellitus increases the susceptibility to encephalitozoonosis in mice

Diabetes mellitus increases the susceptibility to encephalitozoonosis in mice

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

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

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