Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease
The nasal microenvironment plays a crucial role in the transmission, modulation, and clinical progression of COVID-19; however, the immune responses at the site of viral entry remain poorly understood. We deciphered the link between nasopharyngeal (NP) immune and inflammatory response that triggers...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | COVID |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-8112/3/4/41 |
| _version_ | 1797605850335936512 |
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| author | Mohamad Ammar Ayass Trivendra Tripathi Natalya Griko Ramya Ramankutty Nair Jin Zhang Kevin Zhu Wanying Cao Victor Pashkov Tutku Okyay Sharda Kalla Singh Lina Abi-Mosleh |
| author_facet | Mohamad Ammar Ayass Trivendra Tripathi Natalya Griko Ramya Ramankutty Nair Jin Zhang Kevin Zhu Wanying Cao Victor Pashkov Tutku Okyay Sharda Kalla Singh Lina Abi-Mosleh |
| author_sort | Mohamad Ammar Ayass |
| collection | DOAJ |
| description | The nasal microenvironment plays a crucial role in the transmission, modulation, and clinical progression of COVID-19; however, the immune responses at the site of viral entry remain poorly understood. We deciphered the link between nasopharyngeal (NP) immune and inflammatory response that triggers cytokine/chemokine storms in the nasal route of COVID-19-positive patients. We used RT-PCR, multiplex ELISA, flow cytometry, and LC-MS/MS to decipher nasopharyngeal immune perturbations associated with severe COVID-19. In addition, we performed in vitro assays using cultured human monocytes-derived macrophages trained both in the presence and absence of SARS-CoV-2 trimeric spike protein(s) and co-cultured with and without autologous human peripheral blood mononuclear cells (hPBMCs)/total T-cells/CD8 T-cells. In vitro immune perturbations were examined by flow cytometry and LC-MS/MS assays. Our findings confirm that macrophages orchestrate NP immune inflammatory responses and highlight the cytokine/chemokine storms associated with the increased CD8<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>+</mo></msup></semantics></math></inline-formula>T-cells along with Tregs, Th1, and Th17.1 T-helper cells. We observed a correlation between in vitro and nasal findings that trained macrophages, profoundly M2c, differentially promote the inflammatory surfactome on CD8 T-cells, including ITGAM, LGALS3, CD38, TKT, LRPAP1, and SSBP1. The findings of this study conclude that inflammatory lymphocyte perturbations within the nasopharynx of COVID-19 patients may enforce immune homeostasis during SARS-CoV-2-infection and contribute to COVID-19 pathology. This study explored the therapeutic target proteins that could facilitate the development of new medications, which could allow for immediate treatment of possible emerging viral infections. |
| first_indexed | 2024-03-11T05:06:54Z |
| format | Article |
| id | doaj.art-558855a73755434195eab21ba5cdbb4d |
| institution | Directory Open Access Journal |
| issn | 2673-8112 |
| language | English |
| last_indexed | 2024-03-11T05:06:54Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | COVID |
| spelling | doaj.art-558855a73755434195eab21ba5cdbb4d2023-11-17T18:50:05ZengMDPI AGCOVID2673-81122023-04-013456759110.3390/covid3040041Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 DiseaseMohamad Ammar Ayass0Trivendra Tripathi1Natalya Griko2Ramya Ramankutty Nair3Jin Zhang4Kevin Zhu5Wanying Cao6Victor Pashkov7Tutku Okyay8Sharda Kalla Singh9Lina Abi-Mosleh10Ayass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAAyass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USAThe nasal microenvironment plays a crucial role in the transmission, modulation, and clinical progression of COVID-19; however, the immune responses at the site of viral entry remain poorly understood. We deciphered the link between nasopharyngeal (NP) immune and inflammatory response that triggers cytokine/chemokine storms in the nasal route of COVID-19-positive patients. We used RT-PCR, multiplex ELISA, flow cytometry, and LC-MS/MS to decipher nasopharyngeal immune perturbations associated with severe COVID-19. In addition, we performed in vitro assays using cultured human monocytes-derived macrophages trained both in the presence and absence of SARS-CoV-2 trimeric spike protein(s) and co-cultured with and without autologous human peripheral blood mononuclear cells (hPBMCs)/total T-cells/CD8 T-cells. In vitro immune perturbations were examined by flow cytometry and LC-MS/MS assays. Our findings confirm that macrophages orchestrate NP immune inflammatory responses and highlight the cytokine/chemokine storms associated with the increased CD8<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>+</mo></msup></semantics></math></inline-formula>T-cells along with Tregs, Th1, and Th17.1 T-helper cells. We observed a correlation between in vitro and nasal findings that trained macrophages, profoundly M2c, differentially promote the inflammatory surfactome on CD8 T-cells, including ITGAM, LGALS3, CD38, TKT, LRPAP1, and SSBP1. The findings of this study conclude that inflammatory lymphocyte perturbations within the nasopharynx of COVID-19 patients may enforce immune homeostasis during SARS-CoV-2-infection and contribute to COVID-19 pathology. This study explored the therapeutic target proteins that could facilitate the development of new medications, which could allow for immediate treatment of possible emerging viral infections.https://www.mdpi.com/2673-8112/3/4/41SARS-CoV-2COVID-19nasopharyngeal swabsimmunologyT-helper cellsTh17.1 |
| spellingShingle | Mohamad Ammar Ayass Trivendra Tripathi Natalya Griko Ramya Ramankutty Nair Jin Zhang Kevin Zhu Wanying Cao Victor Pashkov Tutku Okyay Sharda Kalla Singh Lina Abi-Mosleh Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease COVID SARS-CoV-2 COVID-19 nasopharyngeal swabs immunology T-helper cells Th17.1 |
| title | Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease |
| title_full | Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease |
| title_fullStr | Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease |
| title_full_unstemmed | Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease |
| title_short | Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease |
| title_sort | macrophage induced exacerbation of nasopharyngeal inflammatory lymphocytes in covid 19 disease |
| topic | SARS-CoV-2 COVID-19 nasopharyngeal swabs immunology T-helper cells Th17.1 |
| url | https://www.mdpi.com/2673-8112/3/4/41 |
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