Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis
Summary: Neutrophils are vital for immunity against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), yet their heterogeneous nature suggests a complex role in TB pathogenesis. Here, we identify two distinct neutrophil populations based on CD101 expression, highlighting the...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724014232 |
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| author | Mohd Saqib Shreya Das Tanvir N. Nafiz Elizabeth McDonough Poornima Sankar Lokesh K. Mishra Ximeng Zhang Yi Cai Selvakumar Subbian Bibhuti B. Mishra |
| author_facet | Mohd Saqib Shreya Das Tanvir N. Nafiz Elizabeth McDonough Poornima Sankar Lokesh K. Mishra Ximeng Zhang Yi Cai Selvakumar Subbian Bibhuti B. Mishra |
| author_sort | Mohd Saqib |
| collection | DOAJ |
| description | Summary: Neutrophils are vital for immunity against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), yet their heterogeneous nature suggests a complex role in TB pathogenesis. Here, we identify two distinct neutrophil populations based on CD101 expression, highlighting their divergent roles in TB. CD101-negative (CD101−ve) neutrophils, which resemble immature, pro-inflammatory granulocytes, exhibit reduced Mtb phagocytosis compared to their mature, CD101-positive (CD101+ve) counterparts. Our findings reveal that type I interferons (IFN-Is) suppress neutrophil Mtb uptake and drive the recruitment of CD101−ve neutrophils to the lungs. Infiltration of these cells promotes Mtb extracellular persistence, exacerbates epithelial damage, and impairs surfactant production. Furthermore, we demonstrate that granulocyte colony-stimulating factor (G-CSF) and chemokine receptor CXCR2 are essential for the pulmonary accumulation of CD101−ve neutrophils. Our study uncovers a pathogenic role for CD101−ve neutrophils in TB and highlights the IFN-I-dependent recruitment of this functionally compromised immature neutrophil as a driver of TB immunopathogenesis. |
| format | Article |
| id | doaj-art-9e364b84c8ea424f8e2f9346a6112459 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-9e364b84c8ea424f8e2f9346a61124592025-08-20T02:36:58ZengElsevierCell Reports2211-12472025-01-0144111507210.1016/j.celrep.2024.115072Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosisMohd Saqib0Shreya Das1Tanvir N. Nafiz2Elizabeth McDonough3Poornima Sankar4Lokesh K. Mishra5Ximeng Zhang6Yi Cai7Selvakumar Subbian8Bibhuti B. Mishra9Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USADepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USADepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USAGE Healthcare Technology and Innovation Center, GE Research, Niskayuna, NY, USADepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USADepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USAGuangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen, ChinaGuangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen, ChinaPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USADepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA; Corresponding authorSummary: Neutrophils are vital for immunity against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), yet their heterogeneous nature suggests a complex role in TB pathogenesis. Here, we identify two distinct neutrophil populations based on CD101 expression, highlighting their divergent roles in TB. CD101-negative (CD101−ve) neutrophils, which resemble immature, pro-inflammatory granulocytes, exhibit reduced Mtb phagocytosis compared to their mature, CD101-positive (CD101+ve) counterparts. Our findings reveal that type I interferons (IFN-Is) suppress neutrophil Mtb uptake and drive the recruitment of CD101−ve neutrophils to the lungs. Infiltration of these cells promotes Mtb extracellular persistence, exacerbates epithelial damage, and impairs surfactant production. Furthermore, we demonstrate that granulocyte colony-stimulating factor (G-CSF) and chemokine receptor CXCR2 are essential for the pulmonary accumulation of CD101−ve neutrophils. Our study uncovers a pathogenic role for CD101−ve neutrophils in TB and highlights the IFN-I-dependent recruitment of this functionally compromised immature neutrophil as a driver of TB immunopathogenesis.http://www.sciencedirect.com/science/article/pii/S2211124724014232CP: ImmunologyCP: Microbiology |
| spellingShingle | Mohd Saqib Shreya Das Tanvir N. Nafiz Elizabeth McDonough Poornima Sankar Lokesh K. Mishra Ximeng Zhang Yi Cai Selvakumar Subbian Bibhuti B. Mishra Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis Cell Reports CP: Immunology CP: Microbiology |
| title | Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis |
| title_full | Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis |
| title_fullStr | Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis |
| title_full_unstemmed | Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis |
| title_short | Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis |
| title_sort | pathogenic role for cd101 negative neutrophils in the type i interferon mediated immunopathogenesis of tuberculosis |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724014232 |
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