investigating-the-phagocytosis-of-leishmania-using-confocal-microscopy

Investigating the Phagocytosis of <em>Leishmania</em> using Confocal Microscopy

Phagocytosis is an orchestrated process that involves distinct steps: recognition, binding, and internalization. Professional phagocytes take up ...

Gonçalo Moniz Institute

Poorly controlled diabetes mellitus leads to several comorbidities, including susceptibility to infections. Hyperglycemia increases phagocyte responsiveness, however immune cells from people with diabetes show inadequate antimicrobial functions. We and others have shown that aberrant production of leukotriene B (LTB) is detrimental to host defense in models of bacterial infection. Here, we will unveil the consequences of high glucose in the outcome of  skin infection in people with diabetes and determine the role of LTB in human phagocytes. We show that diabetes leads to higher systemic levels of LTB, IL-6 and TNF-α in cutaneous leishmaniasis. Only LTB correlated with blood glucose levels and healing time in diabetes comorbidity. Skin lesions of people with leishmaniasis and diabetes exhibit increased neutrophil and amastigote numbers. Monocyte-derived macrophages from these individuals showed higher  loads, reduced production of Reactive Oxygen Species and unbalanced LTB/PGE ratio. Our data reveal a systemic inflammation driven by diabetes comorbidity in opposition to a local reduced capacity to resolve  infection and a worse disease outcome.

Unbalanced production of LTB/PGE driven by diabetes increases susceptibility to cutaneous leishmaniasis.

Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (/), and for the main molecule of the leukotriene B (LTB) pathway (). We found that diabetes activates the LTB pathway and that during COVID-19 it increases / as well as  expression. Diabetes was also associated with COVID-19-related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO) and arterial partial pressure of oxygen/FiO levels, and increased disease duration. In addition, the expressions of  and  are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB and IL-6 systemic levels, as well as / blood expression, could be early markers of severe COVID-19 in individuals with diabetes.

Article	Year
Unbalanced production of LTB/PGE driven by diabetes increases susceptibility to cutaneous leishmaniasis. Emerging microbes & infections\| PubMed ID: 32525457	2020
LTB-Driven Inflammation and Increased Expression of / During Severe COVID-19 in Individuals With Diabetes. Diabetes\| PubMed ID: 34417262	2021

Natália M. Tavares

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