Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases

Frontiers in Immunology

Immunology

Melina Joshi¹  Richard Adeleke²  Seto Charles Ogunleye³  Qudus Afolabi Akande⁴  Joy Olaoluwa Gbadegoye⁵  Fasilat Oluwakemi Hassan⁵  Ifeoluwa Peace Oladapo⁶  Sammuel Shahzad⁶  Olalekan Chris Akinsulie⁶  Ridwan Olamilekan Adesola⁷  Charles Egede Ugwu⁸ 

[1] Center for Molecular Dynamics Nepal, Kathmandu, Nepal;College of Veterinary Medicine, Cornell University, Ithaca, NY, United States;College of Veterinary Medicine, Mississippi State University, Starkville, MS, United States;Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, United States;Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, United States;Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United States;Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria;Paul G. Allen School for Global Health, Washington State University, Pullman, WA, United States;

关键词: hypoxia;    HIFs;    NF-kB;    immune cells;    infectious diseases;    inflammation;   

DOI  :  10.3389/fimmu.2023.1224102

 received in 2023-05-17, accepted in 2023-06-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

There are overwhelming reports on the promotional effect of hypoxia on the malignant behavior of various forms of cancer cells. This has been proposed and tested exhaustively in the light of cancer immunotherapy. However, there could be more interesting functions of a hypoxic cellular micro-environment than malignancy. There is a highly intricate crosstalk between hypoxia inducible factor (HIF), a transcriptional factor produced during hypoxia, and nuclear factor kappa B (NF‐κB) which has been well characterized in various immune cell types. This important crosstalk shares common activating and inhibitory stimuli, regulators, and molecular targets. Impaired hydroxylase activity contributes to the activation of HIFs. Inflammatory ligands activate NF-κB activity, which leads to the expression of inflammatory and anti-apoptotic genes. The eventual sequelae of the interaction between these two molecular players in immune cells, either bolstering or abrogating functions, is largely cell-type dependent. Importantly, this holds promise for interesting therapeutic interventions against several infectious diseases, as some HIF agonists have helped prevent immune‐related diseases. Hypoxia and inflammation are common features of infectious diseases. Here, we highlighted the role of this crosstalk in the light of functional immunity against infection and inflammation, with special focus on various innate and adaptive immune cells. Particularly, we discussed the bidirectional effects of this crosstalk in the regulation of immune responses by monocytes/macrophages, dendritic cells, neutrophils, B cells, and T cells. We believe an advanced understanding of the interplay between HIFs and NF-kB could reveal novel therapeutic targets for various infectious diseases with limited treatment options.

【 授权许可】

Unknown   
Copyright © 2023 Akinsulie, Shahzad, Ogunleye, Oladapo, Joshi, Ugwu, Gbadegoye, Hassan, Adeleke, Afolabi Akande and Adesola