Human NK cells confer protection against HIV-1 infection in humanized mice
The role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022-12-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI162694 |
| _version_ | 1797634518258024448 |
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| author | Can M. Sungur Qiankun Wang Ayşe N. Ozantürk Hongbo Gao Aaron J. Schmitz Marina Cella Wayne M. Yokoyama Liang Shan |
| author_facet | Can M. Sungur Qiankun Wang Ayşe N. Ozantürk Hongbo Gao Aaron J. Schmitz Marina Cella Wayne M. Yokoyama Liang Shan |
| author_sort | Can M. Sungur |
| collection | DOAJ |
| description | The role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the humanized MISTRG-6-15 mouse model, in which NK cells were quick to expand and exhibit degranulation, cytotoxicity, and proinflammatory cytokine production in nonlymphoid organs upon HIV-1 infection but had reduced functionality in lymphoid organs. Although HIV-1 infection induced functional impairment of NK cells, antiretroviral therapy reinvigorated NK cells in response to HIV-1 rebound after analytic treatment interruption. Moreover, a broadly neutralizing antibody, PGT121, enhanced NK cell function in vivo, consistent with antibody-dependent cellular cytotoxicity. Monoclonal antibody depletion of NK cells resulted in higher viral loads in multiple nonlymphoid organs. Overall, our results in humanized MISTRG-6-15 mice demonstrated that NK cells provided direct anti–HIV-1 responses in vivo but were limited in their responses in lymphoid organs. |
| first_indexed | 2024-03-11T12:09:54Z |
| format | Article |
| id | doaj.art-9b0131221adb45cb99de54bafcf1897f |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:09:54Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-9b0131221adb45cb99de54bafcf1897f2023-11-07T16:19:39ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-12-0113224Human NK cells confer protection against HIV-1 infection in humanized miceCan M. SungurQiankun WangAyşe N. OzantürkHongbo GaoAaron J. SchmitzMarina CellaWayne M. YokoyamaLiang ShanThe role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the humanized MISTRG-6-15 mouse model, in which NK cells were quick to expand and exhibit degranulation, cytotoxicity, and proinflammatory cytokine production in nonlymphoid organs upon HIV-1 infection but had reduced functionality in lymphoid organs. Although HIV-1 infection induced functional impairment of NK cells, antiretroviral therapy reinvigorated NK cells in response to HIV-1 rebound after analytic treatment interruption. Moreover, a broadly neutralizing antibody, PGT121, enhanced NK cell function in vivo, consistent with antibody-dependent cellular cytotoxicity. Monoclonal antibody depletion of NK cells resulted in higher viral loads in multiple nonlymphoid organs. Overall, our results in humanized MISTRG-6-15 mice demonstrated that NK cells provided direct anti–HIV-1 responses in vivo but were limited in their responses in lymphoid organs.https://doi.org/10.1172/JCI162694Immunology |
| spellingShingle | Can M. Sungur Qiankun Wang Ayşe N. Ozantürk Hongbo Gao Aaron J. Schmitz Marina Cella Wayne M. Yokoyama Liang Shan Human NK cells confer protection against HIV-1 infection in humanized mice The Journal of Clinical Investigation Immunology |
| title | Human NK cells confer protection against HIV-1 infection in humanized mice |
| title_full | Human NK cells confer protection against HIV-1 infection in humanized mice |
| title_fullStr | Human NK cells confer protection against HIV-1 infection in humanized mice |
| title_full_unstemmed | Human NK cells confer protection against HIV-1 infection in humanized mice |
| title_short | Human NK cells confer protection against HIV-1 infection in humanized mice |
| title_sort | human nk cells confer protection against hiv 1 infection in humanized mice |
| topic | Immunology |
| url | https://doi.org/10.1172/JCI162694 |
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