IFN-γ production downstream of NKT cell activation in mice infected with influenza virus enhances the cytolytic activities of both NK cells and viral antigen-specific CD8+ T cells

Ishikawa, Hajime; Tanaka, Kazuo; Kutsukake, Etsuko; Fukui, Toshie; Sasaki, Hiraku; Hata, Akihiko; Noda, Shinichi; Matsumoto, Tetsuya

doi:10.1016/j.virol.2010.08.030

Cited by 56 publications

(49 citation statements)

References 38 publications

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“…Thus, iNKT cell deficiency accelerates lung injury and the fatal outcome in our system. This finding is in agreement with other studies reporting beneficial effects of NKT cells, including iNKT cells, during acute respiratory viral infection (20,34,35) and suggests that iNKT cells play a part in the control of airway inflammation and susceptibility to IAV (H3N2)-associated mortality. The exact mechanisms by which iNKT cells attenuate IAV pathogenesis are yet to be defined.…”

Section: Discussionsupporting

confidence: 93%

Potential Role of Invariant NKT Cells in the Control of Pulmonary Inflammation and CD8+ T Cell Response during Acute Influenza A Virus H3N2 Pneumonia

Paget

Ivanov

Fontaine

et al. 2011

The Journal of Immunology

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Influenza A virus (IAV) infection results in a highly contagious respiratory illness leading to substantial morbidity and occasionally death. In this report, we assessed the in vivo physiological contribution of invariant NKT (iNKT) lymphocytes, a subset of lipid-reactive αβ T lymphocytes, on the host response and viral pathogenesis using a virulent, mouse-adapted, IAV H3N2 strain. Upon infection with a lethal dose of IAV, iNKT cells become activated in the lungs and bronchoalveolar space to become rapidly anergic to further restimulation. Relative to wild-type animals, C57BL/6 mice deficient in iNKT cells (Jα18−/− mice) developed a more severe bronchopneumonia and had an accelerated fatal outcome, a phenomenon reversed by the adoptive transfer of NKT cells prior to infection. The enhanced pathology in Jα18−/− animals was not associated with either reduced or delayed viral clearance in the lungs or with a defective local NK cell response. In marked contrast, Jα18−/− mice displayed a dramatically reduced IAV-specific CD8+ T cell response in the lungs and in lung-draining mediastinal lymph nodes. We further show that this defective CD8+ T cell response correlates with an altered accumulation and maturation of pulmonary CD103+, but not CD11bhigh, dendritic cells in the mediastinal lymph nodes. Taken together, these findings point to a role for iNKT cells in the control of pneumonia as well as in the development of the CD8+ T cell response during the early stage of acute IAV H3N2 infection.

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Section: Discussionsupporting

confidence: 93%

Potential Role of Invariant NKT Cells in the Control of Pulmonary Inflammation and CD8+ T Cell Response during Acute Influenza A Virus H3N2 Pneumonia

Paget

Ivanov

Fontaine

et al. 2011

The Journal of Immunology

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“…Our initial observation that both immature and mature CD1d KO mice were more susceptible to intra-vaginal HSV-2 infection than WT mice is supported by Ashkar and Rosenthal (2003), who found CD1d KO mice to be 10-fold more susceptible to vaginal HSV-2 infection than WT mice. Similar findings have been made for HSV-1, influenza virus and encephalomyocarditis virus infections (GruborBauk et al, 2003;Ishikawa et al, 2010;Exley et al, 2003).…”

Section: Discussionsupporting

confidence: 80%

“…In addition, NKT cells have cytolytic activities owing to expression of granzyme B, perforin, and FasL (Wu et al, 2009). There is increasing evidence that NKT cell-dependent activation of NK cells play a central role in the protective mechanisms (Ishikawa et al, 2010;Exley et al, 2003). This is supported by the finding that specific activation of NKT cells leads to activation of NK cells and that this response is lost in CD1d KO mice (Carnaud et al, 1999;Eberl and MacDonald, 2000).…”

Section: Discussionmentioning

confidence: 97%

NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

et al. 2015

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“…Two previous murine studies showed that α-GalCer administered by intraperitoneal (i.p.) injection increased survival in mice infected with a lethal dose of the IAV A/PR8/342122. A third study found that weight profile and viral titers improved in mice infected with a non-lethal dose of the human IAV E61-13-H17 when α-GalCer was administered i.p., but not through the intranasal route23.…”

Section: Discussionmentioning

confidence: 96%

Rapid control of pandemic H1N1 influenza by targeting NKT-cells

Artiaga

Yang

Hutchinson

et al. 2016

Sci Rep

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Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses. We show that intranasal but not systemic administration of α-GalCer to piglets infected with pandemic A/California/04/2009 (CA04) H1N1 IAV ameliorated disease symptoms and resulted in the restoration of weight gain to the level of uninfected pigs. Correspondingly, viral titers in the upper-and lower-respiratory tract were reduced only in piglets that had received intranasal α-GalCer. Most significantly, lung inflammation as a consequence of virus persistence was largely prevented when NKT-cells were targeted via the respiratory route. Thus, targeting mucosal NKT-cells may provide a novel and potent platform for improving the course of disease in swine infected with seasonal and pandemic influenza viruses, and leads to the suggestion that this may also be true in humans and therefore deserves further study.

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IFN-γ production downstream of NKT cell activation in mice infected with influenza virus enhances the cytolytic activities of both NK cells and viral antigen-specific CD8+ T cells

Cited by 56 publications

References 38 publications

Potential Role of Invariant NKT Cells in the Control of Pulmonary Inflammation and CD8+ T Cell Response during Acute Influenza A Virus H3N2 Pneumonia

Potential Role of Invariant NKT Cells in the Control of Pulmonary Inflammation and CD8+ T Cell Response during Acute Influenza A Virus H3N2 Pneumonia

NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

Rapid control of pandemic H1N1 influenza by targeting NKT-cells

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