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

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

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12 Scopus citations

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.

Original languageEnglish (US)
Article numbere59599
JournalPloS one
Volume8
Issue number3
DOIs
StatePublished - Mar 15 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Maazi, H., Singh, A. K., Speak, A. O., Lombardi, V., Lam, J., Khoo, B., Inn, K. S., Sharpe, A. H., Jung, J. U., & Akbari, O. (2013). Lack of PD-L1 Expression by iNKT Cells Improves the Course of Influenza A Infection. PloS one, 8(3), [e59599]. https://doi.org/10.1371/journal.pone.0059599