Invariant NKT cells reduce the immunosuppressive activity of influenza A virus–induced myeloid-derived suppressor cells in mice and humans

Santo, Carmela De; Salio, Mariolina; Masri, S. Hajar; Lee, Laurel Yong Hwa; Dong, Tao; Speak, Anneliese O.; Porubský, Štefan; Booth, Sarah; Veerapen, Natacha; Besra, Gurdyal S.; Gröne, Hermann Josef; Platt, Frances M.; Zambon, Maria; Cerundolo, Vincenzo

doi:10.1172/jci36264

Cited by 310 publications

(355 citation statements)

References 81 publications

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“…In contrast to experimental models involving other viruses, [27][28][29][30][31] iNKT cell deficiency did not lead to impaired containment and clearance of DENV in the liver and spleen in our experimental system. This finding is not without precedent because iNKT cells have been shown to be dispensable to control the virus load in some experimental systems.…”

Section: Discussioncontrasting

confidence: 87%

“…Several experimental models have highlighted the beneficial role of iNKT cells in virus-associated inflammatory responses. [27][28][29][30][31][32] However, they can also contribute to the immunopathogenesis of viral diseases. For example, using an experimental mouse model of chronic lung disease triggered by infection with Sendai virus, Kim et al 33 demonstrated that IL-13 production by iNKT cells contributes to pulmonary disease.…”

Section: Discussionmentioning

confidence: 99%

“…After comparison of the phenotypes of J␣18 Ϫ/Ϫ and wild-type (WT) animals, it was reported that the role of iNKT cells during experimental viral infection can vary according to the virus and experimental conditions. 20,24 -26 For example, during infection with influenza A virus, herpes simplex virus types 1 and 2, and lymphocytic choriomeningitis virus, iNKT cells have a positive role in anti-viral immune responses and virus-associated disease, [27][28][29][30][31][32] whereas during infection with Sendai virus and herpes simplex virus type 2 (only in aged mice), iNKT cells are rather deleterious. 33,34 However, iNKT cells do not seem to participate in anti-viral immunity or control of viral replication during infection with encephalomyocarditis virus and murine cytomegalovirus.…”

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confidence: 99%

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A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

Renneson¹,

Guabiraba²,

Maillet³

et al. 2011

The American Journal of Pathology

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Dengue virus (DENV), a member of the mosquitoborne flaviviruses, is a serious public health problem in many tropical countries. We assessed the in vivo physiologic contribution of invariant natural killer T (iNKT) cells, a population of nonconventional lipidreactive ␣␤ T lymphocytes, to the host response during experimental DENV infection. We used a mouseadapted DENV serotype 2 strain that causes a disease that resembles severe dengue in humans. On DENV challenge, splenic and hepatic iNKT cells became activated insofar as CD69 and Fas ligand up-regulation and interferon-␥ production. C57BL/6 mice deficient in iNKT cells (J␣18 ؊/؊ ) were more resistant to lethal infection than were wild-type animals, and the phe Dengue virus (DENV), a flavivirus of the Flaviviridae family, is a serious public health problem in tropical and subtropical areas. In the last 60 years, the incidence, distribution, and clinical severity of dengue-related diseases have increased dramatically. 1,2 There are an estimated 50 million to 100 million DENV infections each year, of which approximately 500,000 are severe dengue hemorrhagic fever, and 24,000 result in death. 2,3 DENV is a single-stranded RNA virus that is transmitted to humans by Aedes mosquitoes, primarily Aedes aegypti. Infection with any of the four serotypes of DENV results in clinical symptoms that range from classic dengue fever to severe dengue hemorrhagic fever and shock syndrome, as defined by the World Health Organization. 4 Severe forms are life-threatening and are characterized by hemorrhagic manifestations, hemoconcentration, thrombocytopenia, and increased vascular permeability. 1,5-10 Despite growing public health concerns, currently there is no vaccine and no specific theraSupported in part by the

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Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

Renneson¹,

Guabiraba²,

Maillet³

et al. 2011

The American Journal of Pathology

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“…Several previous studies have demonstrated that the deficiency of iNKT cells leads to the greater susceptibility to certain viral infections (De Santo et al, 2008;Grubor-Bauk et al, 2003;Ilyinskii et al, 2006). These results were supported by the fact that animals with the stimulation of iNKT cells through CD1d pulsed with antigen (KRN 7000) were more resistance to specific viral infections Kakimi et al, 2000;van Dommelen et al, 2003).…”

Section: Discussionmentioning

confidence: 78%

“…The phenotype of CD1d-deficient mice is much more susceptible to different types of viral infection (De Santo et al, 2008;Grubor-Bauk et al, 2003;Ilyinskii et al, 2006). In addition, activation of iNKT cells by α-galactosylceramide (KRN 7000) through presentation by CD1d enhances the protection of host animals during several tested viral infections Kakimi et al, 2000;van Dommelen et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Human Cytomegalovirus (HCMV) US2 Protein Interacts with Human CD1d (hCD1d) and Down-Regulates Invariant NKT (iNKT) Cell Activity

Han

Rho

Lee

et al. 2013

Molecules and Cells

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To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-membrane glycoprotein US2, which interferes with antigen presenting mechanism of major histocompatibility complex (MHC) class Ia and class II molecules. However, not many attempts have been made to study the effect of HCMV US2 on the expression of MHC class Ib molecules. In this study, we examined the effect of HCMV US2 on the expression and function of human CD1d (hCD1d), which presents glycolipid antigens to invariant NKT (iNKT) cells. Our results clearly showed that the physiological interaction between ER lumenal domain of HCMV US2 and α3 domain of hCD1d was observed within ER. Compared with mature form of hCD1d, immature form of hCD1d is more susceptible to ubiquitin-dependent proteasomal degradation mediated by HCMV US2. Moreover, the ectopic expression of HCMV US2 leads to the down-modulation of iNKT cell activity without significant change of hCD1d expression. These results will advance our understanding of the function of HCMV US2 in immune evasive mechanisms against anti-viral immunity of iNKT cells.

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CD1d ‐Restricted Natural Killer T Cells

Hill

Bezbradica

Kaer

et al. 2016

Encyclopedia of Life Sciences

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Natural killer T (NKT) cells that express the semi‐invariant T‐cell receptor are innate‐like lymphocytes whose functions are controlled by self and foreign glycolipid ligands. Such ligands are presented by the antigen‐presenting, MHC class I‐like molecule CD1d, which belongs to a family of lipid antigen‐presenting molecules collectively called CD1. Activation of NKT cells in vivo results in rapid release of copious amounts of effector cytokines and chemokines with which they regulate innate and adaptive immune responses to pathogens, certain types of cancers and self‐antigens. The nature of CD1d‐restricted ligands, the manners in which they are recognised and the unique effector functions of NKT cells suggest an immunoregulatory role for this T‐cell subset. Their ability to respond fast and our ability to steer NKT cell cytokine responses to altered lipid ligands make them an important target for vaccine design and immunotherapies against autoimmune diseases. This article summarises our current understanding of CD1d‐restricted NKT cell biology and how these innate‐like lymphocytes control inflammation. Key Concepts CD1d molecules belong to a family of lipid antigen‐presenting molecules collectively called CD1. CD1d molecules resemble peptide antigen‐presenting MHC class I molecules. CD1d molecules restrict the specificity and functions of Natural killer T (NKT) cells. NKT cells recognise self‐ and nonself‐lipid ligands. Antigen recognition quickly activates NKT cells, which respond immediately by releasing proinflammatory and immunoregulatory cytokines and chemokines. Activated NKT cells communicate with cells of the innate and adaptive immune systems by cell–cell interactions and/or via soluble mediators. Such communications allow NKT cells to control immune responses to microbial pathogens and certain cancers. NKT‐cell activation has beneficial and, sometimes, adverse effects on certain autoimmune and metabolic disorders. NKT cells are targets for vaccine adjuvants and immunotherapies.

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Invariant NKT cells reduce the immunosuppressive activity of influenza A virus–induced myeloid-derived suppressor cells in mice and humans

Cited by 310 publications

References 81 publications

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

Human Cytomegalovirus (HCMV) US2 Protein Interacts with Human CD1d (hCD1d) and Down-Regulates Invariant NKT (iNKT) Cell Activity

CD1d ‐Restricted Natural Killer T Cells

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