4.5 Article

Impairment of effector molecules response in diabetes induces susceptibility to Leishmania amazonensis infection

期刊

IMMUNOLOGY LETTERS
卷 237, 期 -, 页码 58-65

出版社

ELSEVIER
DOI: 10.1016/j.imlet.2021.07.001

关键词

Type 2 Diabetes; Leishmaniasis; PBMC; NRF2; Oxidative stress

资金

  1. Fundacao Araucaria de Apoio ao Desenvolvimento Cientifico e Tecnologico do Estado do Parana [PBA2016 - CP 09/2016 - PROPPG 03/2016]

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The study found that peripheral blood mononuclear cells (PBMC) from diabetic patients are more susceptible to L. amazonensis infection and fail to control the infection over time due to an inability to generate effector microbicidal molecules, which results in oxidative stress and dysregulated inflammatory response.
Type 2 Diabetes is a chronic disease resulting from insulin dysfunction that triggers a low-grade inflammatory state and immune impairment. Leishmaniasis is an infectious disease characterized by chronic inflammation resulted from the parasite's immunomodulation ability. Thus, due to the delicate immune balance required in the combat and resistance to Leishmania infection and the chronic deregulation of the inflammatory response observed in type 2 diabetes, we evaluated the response of PBMC from diabetic patients to in vitro Leishmania amazonensis infection. For that, peripheral blood was collected from 25 diabetic patients and 25 healthy controls matched for age for cells extraction and subsequent experimental infection for 2 or 24 h and analyzed for phagocytic and leishmanicidal capacity by optical microscopy, oxidative stress by GSSG generation, labeling of intracellular mediators by enzyme-Linked immunosorbent assay, and cytokines measurement with cytometric beads array technique. We found that the diabetic group had a higher percentage of infected cells and a greater number of amastigotes per cell. Also, even inducing NF-kB phosphorylation and increasing TNF production after infection, cells from diabetic patients were unable to downregulate NRF2 and generate oxidative stress, which may be associated with the exacerbated levels of IL-6 observed. PBMC of diabetic individuals are more susceptible to infection by L. amazonensis and fail to control the infection over time due to the inability to generate effector microbicidal molecules.

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