Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells
Lung macrophage (LM) is vital in host defence against bacterial infections. However, the influence of other innate immune cells on its function, including the polarisation of different subpopulations, remains poorly understood. This study examined the polarisation of LM subpopulations (monocytes/und...
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MDPI AG
2024-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/2/133 |
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| author | Ying Peng Sai Qiao Hong Wang Sudhanshu Shekhar Shuhe Wang Jie Yang Yijun Fan Xi Yang |
| author_facet | Ying Peng Sai Qiao Hong Wang Sudhanshu Shekhar Shuhe Wang Jie Yang Yijun Fan Xi Yang |
| author_sort | Ying Peng |
| collection | DOAJ |
| description | Lung macrophage (LM) is vital in host defence against bacterial infections. However, the influence of other innate immune cells on its function, including the polarisation of different subpopulations, remains poorly understood. This study examined the polarisation of LM subpopulations (monocytes/undifferentiated macrophages (Mo/Mφ), interstitial macrophages (IM), and alveolar macrophages (AM)). We further assessed the effect of invariant natural killer T cells (iNKT) on LM polarisation in a protective function against <i>Chlamydia muridarum</i>, an obligate intracellular bacterium, and respiratory tract infection. We found a preferentially increased local Mo/Mφ and IMs with a significant shift to a type-1 macrophage (M1) phenotype and higher expression of iNOS and TNF-α. Interestingly, during the same infection, the alteration of macrophage subpopulations and the shift towards M1 was much less in iNKT KO mice. More importantly, functional testing by adoptively transferring LMs isolated from iNKT KO mice (iNKT KO-Mφ) conferred less protection than those isolated from wild-type mice (WT-Mφ). Further analyses showed significantly reduced gene expression of the JAK/STAT signalling pathway molecules in iNKT KO-Mφ. The data show an important role of iNKT in promoting LM polarisation to the M1 direction, which is functionally relevant to host defence against a human intracellular bacterial infection. The alteration of JAK/STAT signalling molecule gene expression in iNKT KO-Mφ suggests the modulating effect of iNKT is likely through the JAK/STAT pathway. |
| first_indexed | 2024-03-08T09:55:37Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T09:55:37Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2c07c7e8c9094a60843638d20319af0b2024-01-29T13:50:16ZengMDPI AGCells2073-44092024-01-0113213310.3390/cells13020133Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T CellsYing Peng0Sai Qiao1Hong Wang2Sudhanshu Shekhar3Shuhe Wang4Jie Yang5Yijun Fan6Xi Yang7Department of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDepartment of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDepartment of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDepartment of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDepartment of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDepartment of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDepartment of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDepartment of Immunology, Rady Max College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaLung macrophage (LM) is vital in host defence against bacterial infections. However, the influence of other innate immune cells on its function, including the polarisation of different subpopulations, remains poorly understood. This study examined the polarisation of LM subpopulations (monocytes/undifferentiated macrophages (Mo/Mφ), interstitial macrophages (IM), and alveolar macrophages (AM)). We further assessed the effect of invariant natural killer T cells (iNKT) on LM polarisation in a protective function against <i>Chlamydia muridarum</i>, an obligate intracellular bacterium, and respiratory tract infection. We found a preferentially increased local Mo/Mφ and IMs with a significant shift to a type-1 macrophage (M1) phenotype and higher expression of iNOS and TNF-α. Interestingly, during the same infection, the alteration of macrophage subpopulations and the shift towards M1 was much less in iNKT KO mice. More importantly, functional testing by adoptively transferring LMs isolated from iNKT KO mice (iNKT KO-Mφ) conferred less protection than those isolated from wild-type mice (WT-Mφ). Further analyses showed significantly reduced gene expression of the JAK/STAT signalling pathway molecules in iNKT KO-Mφ. The data show an important role of iNKT in promoting LM polarisation to the M1 direction, which is functionally relevant to host defence against a human intracellular bacterial infection. The alteration of JAK/STAT signalling molecule gene expression in iNKT KO-Mφ suggests the modulating effect of iNKT is likely through the JAK/STAT pathway.https://www.mdpi.com/2073-4409/13/2/133<i>Chlamydia</i>macrophageiNKT cellsM1JAK/STAT signalling pathway |
| spellingShingle | Ying Peng Sai Qiao Hong Wang Sudhanshu Shekhar Shuhe Wang Jie Yang Yijun Fan Xi Yang Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells Cells <i>Chlamydia</i> macrophage iNKT cells M1 JAK/STAT signalling pathway |
| title | Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells |
| title_full | Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells |
| title_fullStr | Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells |
| title_full_unstemmed | Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells |
| title_short | Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells |
| title_sort | enhancement of macrophage immunity against chlamydial infection by natural killer t cells |
| topic | <i>Chlamydia</i> macrophage iNKT cells M1 JAK/STAT signalling pathway |
| url | https://www.mdpi.com/2073-4409/13/2/133 |
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