Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection.
There is evidence indicating that invariant Natural Killer T (iNKT) cells play an important role in defense against influenza A virus (IAV). However, the effect of inhibitory receptor, programmed death-1 (PD-1), and its ligands, programmed death ligand (PD-L) 1 and 2 on iNKT cells in protection agai...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3598698?pdf=render |
| _version_ | 1811196881456332800 |
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| author | Hadi Maazi Abinav K Singh Anneliese O Speak Vincent Lombardi Jonathan Lam Bryant Khoo Kyung Soo Inn Arlene H Sharpe Jae U Jung Omid Akbari |
| author_facet | Hadi Maazi Abinav K Singh Anneliese O Speak Vincent Lombardi Jonathan Lam Bryant Khoo Kyung Soo Inn Arlene H Sharpe Jae U Jung Omid Akbari |
| author_sort | Hadi Maazi |
| collection | DOAJ |
| description | There is evidence indicating that invariant Natural Killer T (iNKT) cells play an important role in defense against influenza A virus (IAV). However, the effect of inhibitory receptor, programmed death-1 (PD-1), and its ligands, programmed death ligand (PD-L) 1 and 2 on iNKT cells in protection against IAV remains to be elucidated. Here we investigated the effects of these co-stimulatory molecules on iNKT cells in the response to influenza. We discovered that compare to the wild type, PD-L1 deficient mice show reduced sensitivity to IAV infection as evident by reduced weight loss, decreased pulmonary inflammation and cellular infiltration. In contrast, PD-L2 deficient mice showed augmented weight loss, pulmonary inflammation and cellular infiltration compare to the wild type mice after influenza infection. Adoptive transfer of iNKT cells from wild type, PD-L1 or PD-L2 deficient mice into iNKT cell deficient mice recapitulated these findings. Interestingly, in our transfer system PD-L1(-/-)-derived iNKT cells produced high levels of interferon-gamma whereas PD-L2(-/-)-derived iNKT cells produced high amounts of interleukin-4 and 13 suggesting a role for these cytokines in sensitivity to influenza. We identified that PD-L1 negatively regulates the frequency of iNKT cell subsets in the lungs of IAV infected mice. Altogether, these results demonstrate that lack of PD-L1 expression by iNKT cells reduces the sensitivity to IAV and that the presence of PD-L2 is important for dampening the deleterious inflammatory responses after IAV infection. Our findings potentially have clinical implications for developing new therapies for influenza. |
| first_indexed | 2024-04-12T01:07:28Z |
| format | Article |
| id | doaj.art-15a3311e617f4a77807158ecf273ae2d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T01:07:28Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-15a3311e617f4a77807158ecf273ae2d2022-12-22T03:54:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5959910.1371/journal.pone.0059599Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection.Hadi MaaziAbinav K SinghAnneliese O SpeakVincent LombardiJonathan LamBryant KhooKyung Soo InnArlene H SharpeJae U JungOmid AkbariThere is evidence indicating that invariant Natural Killer T (iNKT) cells play an important role in defense against influenza A virus (IAV). However, the effect of inhibitory receptor, programmed death-1 (PD-1), and its ligands, programmed death ligand (PD-L) 1 and 2 on iNKT cells in protection against IAV remains to be elucidated. Here we investigated the effects of these co-stimulatory molecules on iNKT cells in the response to influenza. We discovered that compare to the wild type, PD-L1 deficient mice show reduced sensitivity to IAV infection as evident by reduced weight loss, decreased pulmonary inflammation and cellular infiltration. In contrast, PD-L2 deficient mice showed augmented weight loss, pulmonary inflammation and cellular infiltration compare to the wild type mice after influenza infection. Adoptive transfer of iNKT cells from wild type, PD-L1 or PD-L2 deficient mice into iNKT cell deficient mice recapitulated these findings. Interestingly, in our transfer system PD-L1(-/-)-derived iNKT cells produced high levels of interferon-gamma whereas PD-L2(-/-)-derived iNKT cells produced high amounts of interleukin-4 and 13 suggesting a role for these cytokines in sensitivity to influenza. We identified that PD-L1 negatively regulates the frequency of iNKT cell subsets in the lungs of IAV infected mice. Altogether, these results demonstrate that lack of PD-L1 expression by iNKT cells reduces the sensitivity to IAV and that the presence of PD-L2 is important for dampening the deleterious inflammatory responses after IAV infection. Our findings potentially have clinical implications for developing new therapies for influenza.http://europepmc.org/articles/PMC3598698?pdf=render |
| spellingShingle | Hadi Maazi Abinav K Singh Anneliese O Speak Vincent Lombardi Jonathan Lam Bryant Khoo Kyung Soo Inn Arlene H Sharpe Jae U Jung Omid Akbari Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. PLoS ONE |
| title | Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. |
| title_full | Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. |
| title_fullStr | Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. |
| title_full_unstemmed | Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. |
| title_short | Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. |
| title_sort | lack of pd l1 expression by inkt cells improves the course of influenza a infection |
| url | http://europepmc.org/articles/PMC3598698?pdf=render |
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