Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases
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-environm...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1224102/full |
| _version_ | 1797756011808817152 |
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| author | Olalekan Chris Akinsulie Sammuel Shahzad Seto Charles Ogunleye Ifeoluwa Peace Oladapo Melina Joshi Charles Egede Ugwu Joy Olaoluwa Gbadegoye Fasilat Oluwakemi Hassan Richard Adeleke Qudus Afolabi Akande Ridwan Olamilekan Adesola |
| author_facet | Olalekan Chris Akinsulie Sammuel Shahzad Seto Charles Ogunleye Ifeoluwa Peace Oladapo Melina Joshi Charles Egede Ugwu Joy Olaoluwa Gbadegoye Fasilat Oluwakemi Hassan Richard Adeleke Qudus Afolabi Akande Ridwan Olamilekan Adesola |
| author_sort | Olalekan Chris Akinsulie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T17:55:24Z |
| format | Article |
| id | doaj.art-4bc2b69ce0be4952a2a24d6809d8a249 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T17:55:24Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4bc2b69ce0be4952a2a24d6809d8a2492023-08-02T17:48:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12241021224102Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseasesOlalekan Chris Akinsulie0Sammuel Shahzad1Seto Charles Ogunleye2Ifeoluwa Peace Oladapo3Melina Joshi4Charles Egede Ugwu5Joy Olaoluwa Gbadegoye6Fasilat Oluwakemi Hassan7Richard Adeleke8Qudus Afolabi Akande9Ridwan Olamilekan Adesola10Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesCollege of Veterinary Medicine, Mississippi State University, Starkville, MS, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesCenter for Molecular Dynamics Nepal, Kathmandu, NepalPaul G. Allen School for Global Health, Washington State University, Pullman, WA, United StatesDepartment of Physiology, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Physiology, University of Tennessee Health Science Center, Memphis, TN, United StatesCollege of Veterinary Medicine, Cornell University, Ithaca, NY, United StatesDepartment of Biological Sciences, University of Notre Dame, Notre Dame, IN, United StatesFaculty of Veterinary Medicine, University of Ibadan, Ibadan, Oyo State, NigeriaThere 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1224102/fullhypoxiaHIFsNF-kBimmune cellsinfectious diseasesinflammation |
| spellingShingle | Olalekan Chris Akinsulie Sammuel Shahzad Seto Charles Ogunleye Ifeoluwa Peace Oladapo Melina Joshi Charles Egede Ugwu Joy Olaoluwa Gbadegoye Fasilat Oluwakemi Hassan Richard Adeleke Qudus Afolabi Akande Ridwan Olamilekan Adesola Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases Frontiers in Immunology hypoxia HIFs NF-kB immune cells infectious diseases inflammation |
| title | Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases |
| title_full | Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases |
| title_fullStr | Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases |
| title_full_unstemmed | Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases |
| title_short | Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases |
| title_sort | crosstalk between hypoxic cellular micro environment and the immune system a potential therapeutic target for infectious diseases |
| topic | hypoxia HIFs NF-kB immune cells infectious diseases inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1224102/full |
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