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

Taylon Felipe Silva, Manoela Daiele Gonçalves, Virgínia Márcia Concato, Bruna Taciane da Silva Bortoleti, Fernanda Tomiotto-Pellissier, Raquel Arruda Sanfelice, Ana Carolina Jacob Rodrigues, Mariana Barbosa Detoni, Andréa Name Colado Simão, Luiz Antonio Custodio, Tânia Longo Mazzuco, Idessania Nazareth da Costa, Milena Menegazzo Miranda-Sapla, Wander Rogério Pavanelli, Ivete Conchon-Costa

Journal: Immunology letters 2022;237():58-65

PMID: 34246712

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Laboratory of Immunoparasitology of Neglected Diseases and Cancer-LIDNC, Department of Pathological Sciences, State University of Londrina, Londrina, Brazil. Electronic address: [email protected].; Laboratory of Biotransformation and Phytochemistry, Department of Chemistry, State University of Londrina, Londrina, Brazil.; Laboratory of Immunoparasitology of Neglected Diseases and Cancer-LIDNC, Department of Pathological Sciences, State University of Londrina, Londrina, Brazil.; Laboratory of Immunoparasitology of Neglected Diseases and Cancer-LIDNC, Department of Pathological Sciences, State University of Londrina, Londrina, Brazil; Biosciences and Biotechnology Graduate Program, Carlos Chagas Institute (ICC), Fiocruz, Curitiba, Brazil.; Department of Pathology, Clinical Analysis, and Toxicology, State University of Londrina, Londrina, Brazil.; Endocrine Interactions Research Group, Department of Medical Clinic, State University of Londrina, Londrina, Brazil.; Laboratory of Immunoparasitology of Neglected Diseases and Cancer-LIDNC, Department of Pathological Sciences, State University of Londrina, Londrina, Brazil. Electronic address: [email protected].

DOI: 10.1016/j.imlet.2021.07.001

Link outs

Free resources

Medical:

https://medlineplus.gov/diabetestype2.html

Subscription / membership required

Full Text Sources:

MeSH Terms: Aged, Case-Control Studies, Cytokines, Diabetes Mellitus, Type 2, Disease Susceptibility, Female, Glutathione, Glycated Hemoglobin, Humans, Immunocompetence, In Vitro Techniques, Inflammation, Interleukin-6, Leishmania mexicana, Leishmaniasis, Cutaneous, Leukocytes, Mononuclear, Male, Middle Aged, NF-E2-Related Factor 2, Nitric Oxide, Oxidative Stress, Respiratory Burst, Tumor Necrosis Factor-alpha