Direct and indirect effects of microorganisms on autophagy

Al-Luhaibi Zaid Isam Issa
Direct and indirect effects of microorganisms on autophagy.
[Thesis]

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Abstract in foreign language

Autophagy is an intracellular catabolic process that controls infections both directly and indirectly via its multifaceted effects on the innate and adaptive immune responses. It has been reported that LPS stimulates this cellular process, whereas the effect of IL-36α on autophagy remains largely unknown. We, therefore, investigated how IL-36α modulates the endogenous and LPS-induced autophagy in THP-1 cells. The levels of LC3B-II and autophagic flux were determined by western blotting. The intracellular localization of LC3B was measured by immunofluorescence assay. The activation levels of signaling pathways implicated in autophagy regulation were evaluated by using a phosphokinase array. Our results showed that combined IL-36α and LPS treatment cooperatively increased the levels of LC3B-II and Beclin-1, stimulated the autophagic flux, facilitated intracellular redistribution of LC3B, and increased the average number of autophagosomes per cell. The IL36α/LPS combined treatment increased phosphorylation of STAT5a/b, had minimal effect on the Akt/PRAS40/mTOR pathway, and reduced the levels of phospho-Yes, phospho-FAK, and phospho-WNK1. Thus, this cytokine/PAMP combination triggers pro-autophagic biased signaling by several mechanisms and thus cooperatively stimulates the autophagic cascade. An increased autophagic activity of innate immune cells simultaneously exposed to IL-36α and LPS may play an important role in the pathogenesis of Gram-negative bacterial infections. SARS-CoV-2 can infect and replicate in esophageal cells and enterocytes, leading to direct damage to the intestinal epithelium. The infection decreases the level of angiotensin converting enzyme 2 receptors, thereby altering the composition of the gut microbiota. SARS-CoV-2 elicits a cytokine storm, which contributes to gastrointestinal inflammation. The direct cytopathic effects of SARS-CoV-2, gut dysbiosis, and aberrant immune response result in increased intestinal permeability, which may exacerbate existing symptoms and worsen the prognosis. By exploring the elements of pathogenesis, several therapeutic options have emerged for the treatment of COVID-19 patients, such as biologics and biotherapeutic agents. However, the presence of SARS-CoV-2 in the feces may facilitate the spread of COVID-19 through fecal-oral transmission and contaminate the environment. Thus, gastrointestinal SARS-CoV-2 infection has important epidemiological significance. The development of new therapeutic and preventive options is necessary to treat and restrict the spread of this severe and widespread infection more effectively.

Item Type: Thesis (Doktori értekezés)
Creators: Al-Luhaibi Zaid Isam Issa
Subjects: 01. Natural sciences > 01.06. Biological sciences > 01.06.01. Cell biology, microbiology
01. Natural sciences > 01.06. Biological sciences > 01.06.02. Virology
03. Medical and health sciences > 03.01. Basic medicine > 03.01.04. Immunology
Divisions: Doctoral School of Interdisciplinary Sciences
Tudományterület / tudományág: Medicine > Theoretical Medicine
Nyelv: English
Date: 2022. March 04.
Item ID: 11109
A mű MTMT azonosítója: 32855331
doi: https://doi.org/10.14232/phd.11109
Date Deposited: 2021. Dec. 08. 08:02
Last Modified: 2022. Jun. 01. 10:21
URI: https://doktori.bibl.u-szeged.hu/id/eprint/11109
Defence/Citable status: Defended.

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