Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis
Sphingosine-1-phosphate (S-1P) is a key sphingolipid involved in the pathobiology of various respiratory diseases. We have previously demonstrated the significance of S-1P in controlling non-pathogenic mycobacterial infection in macrophages, and here we demonstrate the therapeutic potential of S-1P...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.03085/full |
| _version_ | 1818064531844235264 |
|---|---|
| author | Vinod Nadella Lalita Sharma Pankaj Kumar Pushpa Gupta Umesh D. Gupta Srikant Tripathi Suresh Pothani S. S. Y. H. Qadri Hridayesh Prakash |
| author_facet | Vinod Nadella Lalita Sharma Pankaj Kumar Pushpa Gupta Umesh D. Gupta Srikant Tripathi Suresh Pothani S. S. Y. H. Qadri Hridayesh Prakash |
| author_sort | Vinod Nadella |
| collection | DOAJ |
| description | Sphingosine-1-phosphate (S-1P) is a key sphingolipid involved in the pathobiology of various respiratory diseases. We have previously demonstrated the significance of S-1P in controlling non-pathogenic mycobacterial infection in macrophages, and here we demonstrate the therapeutic potential of S-1P against pathogenic Mycobacterium tuberculosis (H37Rv) in the mouse model of infection. Our study revealed that S-1P is involved in the expression of iNOS proteins in macrophages, their polarization toward M1 phenotype, and secretion of interferon (IFN)-γ during the course of infection. S-1P is also capable of enhancing infiltration of pulmonary CD11b+ macrophages and expression of S-1P receptor-3 (S-1PR3) in the lungs during the course of infection. We further revealed the influence of S-1P on major signaling components of inflammatory signaling pathways during M. tuberculosis infection, thus highlighting antimycobacterial potential of S-1P in animals. Our data suggest that enhancing S-1P levels by sphingolipid mimetic compounds/drugs can be used as an immunoadjuvant for boosting immunity against pathogenic mycobacteria. |
| first_indexed | 2024-12-10T14:37:29Z |
| format | Article |
| id | doaj.art-f21493878fa2403daedfeffb6f991876 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T14:37:29Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f21493878fa2403daedfeffb6f9918762022-12-22T01:44:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-01-011010.3389/fimmu.2019.03085469461Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosisVinod Nadella0Lalita Sharma1Pankaj Kumar2Pushpa Gupta3Umesh D. Gupta4Srikant Tripathi5Suresh Pothani6S. S. Y. H. Qadri7Hridayesh Prakash8Laboratory of Translational Medicine, School of Life Science, University of Hyderabad, Hyderabad, IndiaLaboratory of Translational Medicine, School of Life Science, University of Hyderabad, Hyderabad, IndiaLaboratory of Translational Medicine, School of Life Science, University of Hyderabad, Hyderabad, IndiaDepartment of Experimental Animal Facility, National JALMA Institute for Leprosy and Other Mycobacterial Disease, Agra, IndiaDepartment of Experimental Animal Facility, National JALMA Institute for Leprosy and Other Mycobacterial Disease, Agra, IndiaDepartment of Bacteriology, National Institute of Research in Tuberculosis, Chennai, IndiaNational Animal Resource Facility for Biomedical Research, National Institute of Nutrition, Indian Council of Medical Research Hyderabad, Hyderabad, IndiaNational Animal Resource Facility for Biomedical Research, National Institute of Nutrition, Indian Council of Medical Research Hyderabad, Hyderabad, IndiaLaboratory of Translational Medicine, School of Life Science, University of Hyderabad, Hyderabad, IndiaSphingosine-1-phosphate (S-1P) is a key sphingolipid involved in the pathobiology of various respiratory diseases. We have previously demonstrated the significance of S-1P in controlling non-pathogenic mycobacterial infection in macrophages, and here we demonstrate the therapeutic potential of S-1P against pathogenic Mycobacterium tuberculosis (H37Rv) in the mouse model of infection. Our study revealed that S-1P is involved in the expression of iNOS proteins in macrophages, their polarization toward M1 phenotype, and secretion of interferon (IFN)-γ during the course of infection. S-1P is also capable of enhancing infiltration of pulmonary CD11b+ macrophages and expression of S-1P receptor-3 (S-1PR3) in the lungs during the course of infection. We further revealed the influence of S-1P on major signaling components of inflammatory signaling pathways during M. tuberculosis infection, thus highlighting antimycobacterial potential of S-1P in animals. Our data suggest that enhancing S-1P levels by sphingolipid mimetic compounds/drugs can be used as an immunoadjuvant for boosting immunity against pathogenic mycobacteria.https://www.frontiersin.org/article/10.3389/fimmu.2019.03085/fullsphingolipidstuberculosisS-1P receptorsmacrophage polarizationinnate immunitylungs |
| spellingShingle | Vinod Nadella Lalita Sharma Pankaj Kumar Pushpa Gupta Umesh D. Gupta Srikant Tripathi Suresh Pothani S. S. Y. H. Qadri Hridayesh Prakash Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis Frontiers in Immunology sphingolipids tuberculosis S-1P receptors macrophage polarization innate immunity lungs |
| title | Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis |
| title_full | Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis |
| title_fullStr | Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis |
| title_full_unstemmed | Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis |
| title_short | Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis |
| title_sort | sphingosine 1 phosphate s 1p promotes differentiation of naive macrophages and enhances protective immunity against mycobacterium tuberculosis |
| topic | sphingolipids tuberculosis S-1P receptors macrophage polarization innate immunity lungs |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.03085/full |
| work_keys_str_mv | AT vinodnadella sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT lalitasharma sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT pankajkumar sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT pushpagupta sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT umeshdgupta sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT srikanttripathi sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT sureshpothani sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT ssyhqadri sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis AT hridayeshprakash sphingosine1phosphates1ppromotesdifferentiationofnaivemacrophagesandenhancesprotectiveimmunityagainstmycobacteriumtuberculosis |