MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection.
Mucosal-associated invariant T (MAIT) cells can recognize and respond to some bacterially infected cells. Several in vitro and in vivo models of Mycobacterium tuberculosis (Mtb) infection suggest that MAIT cells can contribute to control of Mtb, but these studies are often cross-sectional and use pe...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008585 |
| _version_ | 1818716658881003520 |
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| author | Amy L Ellis Alexis J Balgeman Erica C Larson Mark A Rodgers Cassaundra Ameel Tonilynn Baranowski Nadean Kannal Pauline Maiello Jennifer A Juno Charles A Scanga Shelby L O'Connor |
| author_facet | Amy L Ellis Alexis J Balgeman Erica C Larson Mark A Rodgers Cassaundra Ameel Tonilynn Baranowski Nadean Kannal Pauline Maiello Jennifer A Juno Charles A Scanga Shelby L O'Connor |
| author_sort | Amy L Ellis |
| collection | DOAJ |
| description | Mucosal-associated invariant T (MAIT) cells can recognize and respond to some bacterially infected cells. Several in vitro and in vivo models of Mycobacterium tuberculosis (Mtb) infection suggest that MAIT cells can contribute to control of Mtb, but these studies are often cross-sectional and use peripheral blood cells. Whether MAIT cells are recruited to Mtb-affected granulomas and lymph nodes (LNs) during early Mtb infection and what purpose they might serve there is less well understood. Furthermore, whether HIV/SIV infection impairs MAIT cell frequency or function at the sites of Mtb replication has not been determined. Using Mauritian cynomolgus macaques (MCM), we phenotyped MAIT cells in the peripheral blood and bronchoalveolar lavage (BAL) before and during infection with SIVmac239. To test the hypothesis that SIV co-infection impairs MAIT cell frequency and function within granulomas, SIV+ and -naïve MCM were infected with a low dose of Mtb Erdman, and necropsied at 6 weeks post Mtb-challenge. MAIT cell frequency and function were examined within the peripheral blood, BAL, and Mtb-affected lymph nodes (LN) and granulomas. MAIT cells did not express markers indicative of T cell activation in response to Mtb in vivo within granulomas in animals infected with Mtb alone. SIV and Mtb co-infection led to increased expression of the activation/exhaustion markers PD-1 and TIGIT, and decreased ability to secrete TNFα when compared to SIV-naïve MCM. Our study provides evidence that SIV infection does not prohibit the recruitment of MAIT cells to sites of Mtb infection, but does functionally impair those MAIT cells. Their impaired function could have impacts, either direct or indirect, on the long-term containment of TB disease. |
| first_indexed | 2024-12-17T19:22:46Z |
| format | Article |
| id | doaj.art-da336923d11e4271be30be209e0ba75c |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-17T19:22:46Z |
| publishDate | 2020-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-da336923d11e4271be30be209e0ba75c2022-12-21T21:35:27ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-05-01165e100858510.1371/journal.ppat.1008585MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection.Amy L EllisAlexis J BalgemanErica C LarsonMark A RodgersCassaundra AmeelTonilynn BaranowskiNadean KannalPauline MaielloJennifer A JunoCharles A ScangaShelby L O'ConnorMucosal-associated invariant T (MAIT) cells can recognize and respond to some bacterially infected cells. Several in vitro and in vivo models of Mycobacterium tuberculosis (Mtb) infection suggest that MAIT cells can contribute to control of Mtb, but these studies are often cross-sectional and use peripheral blood cells. Whether MAIT cells are recruited to Mtb-affected granulomas and lymph nodes (LNs) during early Mtb infection and what purpose they might serve there is less well understood. Furthermore, whether HIV/SIV infection impairs MAIT cell frequency or function at the sites of Mtb replication has not been determined. Using Mauritian cynomolgus macaques (MCM), we phenotyped MAIT cells in the peripheral blood and bronchoalveolar lavage (BAL) before and during infection with SIVmac239. To test the hypothesis that SIV co-infection impairs MAIT cell frequency and function within granulomas, SIV+ and -naïve MCM were infected with a low dose of Mtb Erdman, and necropsied at 6 weeks post Mtb-challenge. MAIT cell frequency and function were examined within the peripheral blood, BAL, and Mtb-affected lymph nodes (LN) and granulomas. MAIT cells did not express markers indicative of T cell activation in response to Mtb in vivo within granulomas in animals infected with Mtb alone. SIV and Mtb co-infection led to increased expression of the activation/exhaustion markers PD-1 and TIGIT, and decreased ability to secrete TNFα when compared to SIV-naïve MCM. Our study provides evidence that SIV infection does not prohibit the recruitment of MAIT cells to sites of Mtb infection, but does functionally impair those MAIT cells. Their impaired function could have impacts, either direct or indirect, on the long-term containment of TB disease.https://doi.org/10.1371/journal.ppat.1008585 |
| spellingShingle | Amy L Ellis Alexis J Balgeman Erica C Larson Mark A Rodgers Cassaundra Ameel Tonilynn Baranowski Nadean Kannal Pauline Maiello Jennifer A Juno Charles A Scanga Shelby L O'Connor MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. PLoS Pathogens |
| title | MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. |
| title_full | MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. |
| title_fullStr | MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. |
| title_full_unstemmed | MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. |
| title_short | MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. |
| title_sort | mait cells are functionally impaired in a mauritian cynomolgus macaque model of siv and mtb co infection |
| url | https://doi.org/10.1371/journal.ppat.1008585 |
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