CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis
Summary: Mycobacterium tuberculosis (Mtb) possesses an arsenal of virulence factors to evade host immunity. Previously, we showed that the Mtb protein CpsA, which protects Mtb against the host NADPH oxidase, is required in mice during the first 3 weeks of infection but is thereafter dispensable for...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723016194 |
| _version_ | 1797383990412312576 |
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| author | Steven J. Grigsby G.V.R. Krishna Prasad Joshua B. Wallach Ekansh Mittal Fong-Fu Hsu Dirk Schnappinger Jennifer A. Philips |
| author_facet | Steven J. Grigsby G.V.R. Krishna Prasad Joshua B. Wallach Ekansh Mittal Fong-Fu Hsu Dirk Schnappinger Jennifer A. Philips |
| author_sort | Steven J. Grigsby |
| collection | DOAJ |
| description | Summary: Mycobacterium tuberculosis (Mtb) possesses an arsenal of virulence factors to evade host immunity. Previously, we showed that the Mtb protein CpsA, which protects Mtb against the host NADPH oxidase, is required in mice during the first 3 weeks of infection but is thereafter dispensable for full virulence. Using flow cytometry, we find that ΔcpsA Mtb is retained in alveolar macrophages, impaired in recruiting and disseminating into monocyte-derived cells, and more likely to be localized in airway cells than wild-type Mtb. The lungs of ΔcpsA-infected mice also have markedly fewer antigen-specific T cells, indicating a delay in adaptive immunity. Thus, we conclude that CpsA promotes dissemination of Mtb from alveolar macrophages and the airways and generation of an adaptive immune response. Our studies of ΔcpsA Mtb show that a more effective innate immune response against Mtb can be undermined by a corresponding delay in the adaptive immune response. |
| first_indexed | 2024-03-08T21:29:55Z |
| format | Article |
| id | doaj.art-3228c02b2160445ab11cf436fc78a962 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-08T21:29:55Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-3228c02b2160445ab11cf436fc78a9622023-12-21T07:32:37ZengElsevierCell Reports2211-12472024-01-01431113607CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosisSteven J. Grigsby0G.V.R. Krishna Prasad1Joshua B. Wallach2Ekansh Mittal3Fong-Fu Hsu4Dirk Schnappinger5Jennifer A. Philips6Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USADivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USADepartment of Microbiology and Immunology, Weill Cornell Medical College, New York City, NY, USADivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USADivision of Endocrinology, Metabolism, & Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USADepartment of Microbiology and Immunology, Weill Cornell Medical College, New York City, NY, USADivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Corresponding authorSummary: Mycobacterium tuberculosis (Mtb) possesses an arsenal of virulence factors to evade host immunity. Previously, we showed that the Mtb protein CpsA, which protects Mtb against the host NADPH oxidase, is required in mice during the first 3 weeks of infection but is thereafter dispensable for full virulence. Using flow cytometry, we find that ΔcpsA Mtb is retained in alveolar macrophages, impaired in recruiting and disseminating into monocyte-derived cells, and more likely to be localized in airway cells than wild-type Mtb. The lungs of ΔcpsA-infected mice also have markedly fewer antigen-specific T cells, indicating a delay in adaptive immunity. Thus, we conclude that CpsA promotes dissemination of Mtb from alveolar macrophages and the airways and generation of an adaptive immune response. Our studies of ΔcpsA Mtb show that a more effective innate immune response against Mtb can be undermined by a corresponding delay in the adaptive immune response.http://www.sciencedirect.com/science/article/pii/S2211124723016194CP: MicrobiologyCP: Immunology |
| spellingShingle | Steven J. Grigsby G.V.R. Krishna Prasad Joshua B. Wallach Ekansh Mittal Fong-Fu Hsu Dirk Schnappinger Jennifer A. Philips CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis Cell Reports CP: Microbiology CP: Immunology |
| title | CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis |
| title_full | CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis |
| title_fullStr | CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis |
| title_full_unstemmed | CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis |
| title_short | CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis |
| title_sort | cpsa mediates infection of recruited lung myeloid cells by mycobacterium tuberculosis |
| topic | CP: Microbiology CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723016194 |
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