Lack of PD-L1 Expression by iNKT Cells Improves the Course of Influenza A Infection

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Lack of PD-L1 Expression by iNKT Cells Improves the Course of Influenza A Infection

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Title: Lack of PD-L1 Expression by iNKT Cells Improves the Course of Influenza A Infection
Author: Maazi, Hadi; Singh, Abinav K.; Speak, Anneliese O.; Lombardi, Vincent; Lam, Jonathan; Khoo, Bryant; Inn, Kyung Soo; Sharpe, Arlene Helen; Jung, Jae U.; Akbari, Omid

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Citation: Maazi, Hadi, Abinav K. Singh, Anneliese O. Speak, Vincent Lombardi, Jonathan Lam, Bryant Khoo, Kyung Soo Inn, Arlene H. Sharpe, Jae U. Jung, and Omid Akbari. 2013. Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. PLoS ONE 8(3): e59599.
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Abstract: 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.
Published Version: doi:10.1371/journal.pone.0059599
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