Insulin Modulates Paracoccidioides brasiliensis-Induced Inflammation by Restoring the Populations of NK Cells, Dendritic Cells, and B Lymphocytes in Lungs

Author(s)

Casagrande, Felipe Beccaria ; Ferreira, Sabrina de Souza ; Barbosa Nunes, Fernanda Peixoto ; Dal'Mas Romera, Lavinia Maria ; dos Santos, Suelen Silvana ; Galvao Tessaro, Fernando Henrique ; Knox de Souza, Paula Regina ; Almeida, Sandro Rogerio ; Martins, Joilson Oliveira

• Document type: Journal article
• Source: JOURNAL OF DIABETES RESEARCH; v. 2018, p. 11-pg., 2018-01-01.

Abstract

Paracoccidioidomycosis, a key issue for Brazilian health service, can be aggravated in patients with impaired immunological responses, such as diabetic patients. We evaluated the role of insulin in inflammatory parameters in diabetic and nondiabetic mice using a systemic mycosis Paracoccidioides brasiliensis (Pb) model. Diabetic C57BL-6 mice and controls were infected with Pb18 and treated with insulin for 12 days prior to experiments. After 55 days, infected diabetic mice exhibited fewer leukocytes in both peritoneal lavage fluid (PeLF) and bronchoalveolar lavage fluid and reduced secretion of interleukin- (IL-) 6 in lungs. In addition, diabetic mice presented a reduced influx of TCD4+ cells, TCD8+ cells, B lymphocytes, NK cells, and dendritic cells compared to control infected groups. Insulin treatment restored the leukocyte number in PeLF and restored the presence of B lymphocytes, dendritic cells, and NK cells in lungs of diabetic animals. The data suggest that diabetic mice present impaired immunological response to Pb18 infection and insulin modulates inflammation by reducing IL-6 levels in lung and CINC-1 levels in spleen and liver homogenates, restoring leukocyte concentrations in PeLF and also restoring populations of dendritic cells and B lymphocytes in lungs of diabetic mice, permitting the host to better control the infection. (AU)

• FAPESP's process: 10/02272-0 - Effect of insulin on lung inflammation in animal with sepsis, innate immunit,activation of insulin gene (BGK) and insulin receptors (IR)-A and IR-B
• Grantee: Joilson de Oliveira Martins
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 12/06617-7 - Role of insulin in the effectiveness of allergic pulmonary inflammation in healthy or diabetic mice
• Grantee: Sabrina de Souza Ferreira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/11540-7 - Investigating the role of insulin in the presence of allergic pulmonary inflammation in diabetic and healthy mice
• Grantee: Joilson de Oliveira Martins
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/06652-7 - CELLULAR AND MOLECULAR ASPECTS INVOLVED IN THE INFLAMMATORY RESPONSE INDUCED BY CARRAGEENAN IN HEALTHY OR DIABETIC MICE
• Grantee: Fernanda Peixoto Barbosa Nunes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/05214-1 - Investigating the role of insulin in different infections in diabetic and healthy animals
• Grantee: Joilson de Oliveira Martins
• Support Opportunities: Regular Research Grants