Leishmania amazonensis infection regulates oxidate stress in hyperglycemia and diabetes impairing macrophage's function and immune response.

Autor: Silva TF; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil. Electronic address: taylonfelipe@hotmail.com., Detoni MB; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Concato-Lopes VM; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Tomiotto-Pellissier F; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil; Department of Medical Pathology, Federal University of Paraná, Curitiba, PR, Brazil., Miranda-Sapla MM; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil; Department of Pharmaceutical Sciences, University of Vale do Itajaí, Itajaí, SC, Brazil., Bortoleti BTDS; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil; Icahn School of Medicine, Mount Sinai Hospital, New York, NY, United States., Gonçalves MD; Biotransformation and Phytochemistry Laboratory, Department of Chemistry, State University of Londrina, Londrina, PR, Brazil., Rodrigues ACJ; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil; Biosciences and Biotechnology Graduate Program, Carlos Chagas Institute (ICC), Fiocruz, Curitiba, PR, Brazil., Sanfelice RA; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Cruz EMS; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Silva MSDS; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Carloto ACM; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Bidoia DL; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Costa IN; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Pavanelli WR; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil., Conchon-Costa I; Laboratory of Immunoparasitology of Neglected Diseases and Cancer (LIDNC), State University of Londrina, Londrina, PR, Brazil. Electronic address: conchon@uel.br.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Apr; Vol. 1870 (4), pp. 167078. Date of Electronic Publication: 2024 Feb 15.
DOI: 10.1016/j.bbadis.2024.167078
Abstrakt: Leishmaniasis is a group of infectious diseases caused by protozoa of the Leishmania genus and its immunopathogenesis results from an unbalanced immune response during the infection. Diabetes is a chronic disease resulting from dysfunction of the body's production of insulin or the ability to use it properly, leading to hyperglycemia causing tissue damage and impairing the immune system.
Aims: The objective of this work was to evaluate the effects of hyperglycemia and diabetes during Leishmania amazonensis infection and how these conditions alter the immune response to the parasite.
Methods: An in vitro hyperglycemic stimulus model using THP-1-derived macrophages and an in vivo experimental diabetes with streptozotocin (STZ) in C57BL/6 mice was employed to investigate the impact of diabetes and hyperglicemia in Leishmania amazonensis infection.
Results: We observed that hyperglycemia impair the leishmanicidal capacity of macrophages derived from THP-1 cells and reverse the resistance profile that C57BL/6 mice have against infection by L. amazonensis, inducing more exacerbated lesions compared to non-diabetic animals. In addition, the hyperglycemic stimulus favored the increase of markers related to the phenotype of M2 macrophages. The induction of experimental diabetes in C57BL/6 mice resulted in a failure in the production of nitric oxide (NO) in the face of infection and macrophages from diabetic animals failed to process and present Leishmania antigens, being unable to activate and induce proliferation of antigen-specific lymphocytes.
Conclusion: Together, these data demonstrate that diabetes and hyperglycemia can impair the cellular immune response, mainly of macrophages, against infection by parasites of the genus Leishmania.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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