TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection.
While T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M. tuberculosis infection. Here we p...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-03-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4788425?pdf=render |
| _version_ | 1811327094570876928 |
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| author | Pushpa Jayaraman Miye K Jacques Chen Zhu Katherine M Steblenko Britni L Stowell Asaf Madi Ana C Anderson Vijay K Kuchroo Samuel M Behar |
| author_facet | Pushpa Jayaraman Miye K Jacques Chen Zhu Katherine M Steblenko Britni L Stowell Asaf Madi Ana C Anderson Vijay K Kuchroo Samuel M Behar |
| author_sort | Pushpa Jayaraman |
| collection | DOAJ |
| description | While T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M. tuberculosis infection. Here we provide functional evidence for the development T cell exhaustion during chronic TB. Second, we evaluate the role of the inhibitory receptor T cell immunoglobulin and mucin domain-containing-3 (TIM3) during chronic M. tuberculosis infection. We find that TIM3 expressing T cells accumulate during chronic infection, co-express other inhibitory receptors including PD1, produce less IL-2 and TNF but more IL-10, and are functionally exhausted. Finally, we show that TIM3 blockade restores T cell function and improves bacterial control, particularly in chronically infected susceptible mice. These data show that T cell immunity is suboptimal during chronic M. tuberculosis infection due to T cell exhaustion. Moreover, in chronically infected mice, treatment with anti-TIM3 mAb is an effective therapeutic strategy against tuberculosis. |
| first_indexed | 2024-04-13T15:00:36Z |
| format | Article |
| id | doaj.art-e500a341367548e1b6b223d3d9e3f61c |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-13T15:00:36Z |
| publishDate | 2016-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-e500a341367548e1b6b223d3d9e3f61c2022-12-22T02:42:18ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-03-01123e100549010.1371/journal.ppat.1005490TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection.Pushpa JayaramanMiye K JacquesChen ZhuKatherine M SteblenkoBritni L StowellAsaf MadiAna C AndersonVijay K KuchrooSamuel M BeharWhile T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M. tuberculosis infection. Here we provide functional evidence for the development T cell exhaustion during chronic TB. Second, we evaluate the role of the inhibitory receptor T cell immunoglobulin and mucin domain-containing-3 (TIM3) during chronic M. tuberculosis infection. We find that TIM3 expressing T cells accumulate during chronic infection, co-express other inhibitory receptors including PD1, produce less IL-2 and TNF but more IL-10, and are functionally exhausted. Finally, we show that TIM3 blockade restores T cell function and improves bacterial control, particularly in chronically infected susceptible mice. These data show that T cell immunity is suboptimal during chronic M. tuberculosis infection due to T cell exhaustion. Moreover, in chronically infected mice, treatment with anti-TIM3 mAb is an effective therapeutic strategy against tuberculosis.http://europepmc.org/articles/PMC4788425?pdf=render |
| spellingShingle | Pushpa Jayaraman Miye K Jacques Chen Zhu Katherine M Steblenko Britni L Stowell Asaf Madi Ana C Anderson Vijay K Kuchroo Samuel M Behar TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection. PLoS Pathogens |
| title | TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection. |
| title_full | TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection. |
| title_fullStr | TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection. |
| title_full_unstemmed | TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection. |
| title_short | TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection. |
| title_sort | tim3 mediates t cell exhaustion during mycobacterium tuberculosis infection |
| url | http://europepmc.org/articles/PMC4788425?pdf=render |
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