Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice
Interleukin-12 receptor β1 (IL12RB1)-deficient individuals show increased susceptibilities to local or disseminated BCG infection and environmental mycobacteria infection. However, the low clinical penetrance of IL12RB1 deficiency and low recurrence rate of mycobacteria infection suggest that protec...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/10/7/1147 |
| _version_ | 1797415096409915392 |
|---|---|
| author | Xuyang Wang Liqiu Jia Yang Liu Jing Wang Chao Qiu Tao Li Wenhong Zhang Zhaoqin Zhu Jing Wu Yanmin Wan |
| author_facet | Xuyang Wang Liqiu Jia Yang Liu Jing Wang Chao Qiu Tao Li Wenhong Zhang Zhaoqin Zhu Jing Wu Yanmin Wan |
| author_sort | Xuyang Wang |
| collection | DOAJ |
| description | Interleukin-12 receptor β1 (IL12RB1)-deficient individuals show increased susceptibilities to local or disseminated BCG infection and environmental mycobacteria infection. However, the low clinical penetrance of IL12RB1 deficiency and low recurrence rate of mycobacteria infection suggest that protective immunity still exists in this population. In this study, we investigated the mechanism of tuberculosis suppression using the IL12RB1-deficient mouse model. Our results manifested that <i>Il12rb1</i><sup>−/−</sup> mice had significantly increased CFU counts in spleens and lungs, especially when BCG (Danish strain) was inoculated subcutaneously. The innate TNF-a and IFN-γ responses decreased, while the IL-17 responses increased significantly in the lungs of <i>Il12rb1</i><sup>−/−</sup> mice. We also found that PPD-specific IFN-γ release was impaired in <i>Il12rb1</i><sup>−/−</sup> mice, but the specific TNF-a release was not compromised, and the antibody responses were significantly enhanced. Moreover, correlation analyses revealed that both the innate and PPD-specific IFN-γ responses positively correlated with CFU counts, whereas the innate IL-12a levels negatively correlated with CFU counts in <i>Il12rb1</i><sup>−/−</sup> mice lungs. Collectively, these findings proved that the adaptive immunities against mycobacteria are not completely nullified in <i>Il12rb1</i><sup>−/−</sup> mice. Additionally, our results imply that IFN-γ responses alone might not be able to contain BCGitis in the setting of IL12RB1 deficiency. |
| first_indexed | 2024-03-09T05:43:08Z |
| format | Article |
| id | doaj.art-5cef8795b6744d5fad0e8ebf78799230 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T05:43:08Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-5cef8795b6744d5fad0e8ebf787992302023-12-03T12:23:30ZengMDPI AGVaccines2076-393X2022-07-01107114710.3390/vaccines10071147Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient MiceXuyang Wang0Liqiu Jia1Yang Liu2Jing Wang3Chao Qiu4Tao Li5Wenhong Zhang6Zhaoqin Zhu7Jing Wu8Yanmin Wan9National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, ChinaNational Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, ChinaShanghai Public Health Clinical Center, Department of Laboratory Medicine, Shanghai 201508, ChinaShanghai Public Health Clinical Center, Department of Laboratory Medicine, Shanghai 201508, ChinaKey Laboratory of Medical Molecular Virology (MOE/MOH), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaShanghai Public Health Clinical Center, Department of Tuberculosis, Shanghai 201508, ChinaNational Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, ChinaShanghai Public Health Clinical Center, Department of Laboratory Medicine, Shanghai 201508, ChinaNational Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, ChinaNational Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, ChinaInterleukin-12 receptor β1 (IL12RB1)-deficient individuals show increased susceptibilities to local or disseminated BCG infection and environmental mycobacteria infection. However, the low clinical penetrance of IL12RB1 deficiency and low recurrence rate of mycobacteria infection suggest that protective immunity still exists in this population. In this study, we investigated the mechanism of tuberculosis suppression using the IL12RB1-deficient mouse model. Our results manifested that <i>Il12rb1</i><sup>−/−</sup> mice had significantly increased CFU counts in spleens and lungs, especially when BCG (Danish strain) was inoculated subcutaneously. The innate TNF-a and IFN-γ responses decreased, while the IL-17 responses increased significantly in the lungs of <i>Il12rb1</i><sup>−/−</sup> mice. We also found that PPD-specific IFN-γ release was impaired in <i>Il12rb1</i><sup>−/−</sup> mice, but the specific TNF-a release was not compromised, and the antibody responses were significantly enhanced. Moreover, correlation analyses revealed that both the innate and PPD-specific IFN-γ responses positively correlated with CFU counts, whereas the innate IL-12a levels negatively correlated with CFU counts in <i>Il12rb1</i><sup>−/−</sup> mice lungs. Collectively, these findings proved that the adaptive immunities against mycobacteria are not completely nullified in <i>Il12rb1</i><sup>−/−</sup> mice. Additionally, our results imply that IFN-γ responses alone might not be able to contain BCGitis in the setting of IL12RB1 deficiency.https://www.mdpi.com/2076-393X/10/7/1147IL12RB1MSMDIFN-γBCGinnate immunityadaptive immunity |
| spellingShingle | Xuyang Wang Liqiu Jia Yang Liu Jing Wang Chao Qiu Tao Li Wenhong Zhang Zhaoqin Zhu Jing Wu Yanmin Wan Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice Vaccines IL12RB1 MSMD IFN-γ BCG innate immunity adaptive immunity |
| title | Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice |
| title_full | Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice |
| title_fullStr | Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice |
| title_full_unstemmed | Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice |
| title_short | Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice |
| title_sort | immune correlates of disseminated bcg infection in il12rb1 deficient mice |
| topic | IL12RB1 MSMD IFN-γ BCG innate immunity adaptive immunity |
| url | https://www.mdpi.com/2076-393X/10/7/1147 |
| work_keys_str_mv | AT xuyangwang immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT liqiujia immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT yangliu immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT jingwang immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT chaoqiu immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT taoli immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT wenhongzhang immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT zhaoqinzhu immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT jingwu immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice AT yanminwan immunecorrelatesofdisseminatedbcginfectioninil12rb1deficientmice |