Activation of hepatic NKT cells and subsequent liver injury following administration of α-galactosylceramide

Osman, Yasser; Kawamura, Toshihiko; Naito, Takaki; Takeda, Kazuyoshi; Kaer, Luc Van; Okumura, Ko; Abo, Toru

doi:10.1002/1521-4141(200007)30:7<1919::aid-immu1919>3.0.co;2-3

Cited by 249 publications

(227 citation statements)

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“…Recovery numbers of HL were also increased by day 4 of L. monocytogenes infection and slightly, though not significantly, elevated by a-GalCer treatment (data not shown). Consistent with previous findings [57][58][59][60][61][62][63][64][65], a-GalCer/CD1d tetramer-reactive (a-GalCer/CD1d 1 ) T cells became undetectable on day 1 after a-GalCer treatment and then re-emerged, though incompletely, by day 4 ( Fig. 2A, Table 1).…”

Section: Monocytogenes-induced Inflammation In the Liver And Spleesupporting

confidence: 92%

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Emoto

Yoshizawa

et al. 2010

Eur J Immunol

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a-Galactosylceramide (a-GalCer) activates invariant (i)NKT cells, which in turn stimulate immunocompetent cells. Although activation of iNKT cells appears critical for regulation of immune responses, it remains elusive whether protection against intracellular bacteria can be induced by a-GalCer. Here, we show that a-GalCer treatment ameliorates murine listeriosis, and inhibits inflammation following Listeria monocytogenes infection. Liver infiltration of Gr-1 1 cells and c/d T cells was accelerated by a-GalCer treatment. Gr-1 1 cell and c/d T-cell depletion exacerbated listeriosis in a-GalCer-treated mice, and this effect was more pronounced after depletion of Gr-1 1 cells than that of c/d T cells. Although GM-CSF and IL-17 were secreted by NKT cells after a-GalCer treatment, liver infiltration of Gr-1 1 cells was not prevented by neutralizing mAb. In parallel to the numerical increase of CD11b 1 Gr-1 1 cells in the liver following a-GalCer treatment, CD11b À Gr-1 1 cells were numerically reduced in the bone marrow. In addition, respiratory burst in Gr-1 1 cells was enhanced by a-GalCer treatment. Our results indicate that a-GalCer-induced antibacterial immunity is caused, in part, by accelerated infiltration of Gr-1 1 cells and to a lesser degree of c/d T cells into the liver. We also suggest that the infiltration of Gr-1 1 cells is caused by an accelerated supply from the bone marrow.Key words: a-galactosylceramide . L. monocytogenes . NKT cell Supporting Information available online IntroductionListeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen, which causes disseminated infection in immunocompromised hosts [1]. Experimental murine listeriosis is instrumental in elucidating host defense mechanisms against intracellular bacteria. Cells of the innate immune system play a pivotal role as a first line of defense against L. monocytogenes [2-5] and among these, Gr-1 1 cells are central for the elimination of this pathogen at early stages of infection [6][7][8]. Numerous cytokines such as GM-CSF, IL-3, IL-6, IL-11, and SCF promote granulopoiesis by themselves and/or in concert with G-CSF [9,10]. G-CSF is indispensable for both steady-state and emergency granulopoiesis [11][12][13][14], and IL-17 regulates G-CSF secretion [9,10,[15][16][17][18]. In addition to Gr-1 1 cells, g/d T cells also participate in early protection against 1328L. monocytogenes infection [19][20][21][22]. The vast majority of L. monocytogenes organisms are trapped in the liver immediately after systemic infection [23] and hence, immunocompetent cells that reside in, and/or migrate into, the liver are critical for infection control.NKT cells represent a unique subset of T lymphocytes, which are characterized by the co-expression of NK cell markers such as NKR-P1B/C (NK1.1; CD161) [24]. In the mouse, the majority of NKT cells express an invariant (i) TCR composed of Va14/Ja18 gene segments, i.e. iNKT cells [24]. In contrast to conventional T cells, which recognize peptide antigens presented by polymorphic MHC ...

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Section: Monocytogenes-induced Inflammation In the Liver And Spleesupporting

confidence: 92%

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Emoto

Yoshizawa

et al. 2010

Eur J Immunol

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“…Interestingly, a recent report by Chisari and colleagues (31) found that the activation of NKT cells in HBV transgenic mice in vivo by ␣-GalCer (a glycolipid that is presented by CD1d1 to NKT cells) (8,9,12,33) caused the rapid loss of NKT cells, recruited NK cells, and inhibited HBV replication in the mice in an IFN-␣/␤-and IFN-␥-dependent manner (31). Others have also seen such a reduction in liver NKT cells following treatment of mice with ␣-GalCer (19,43,48) or anti-CD3 (18) and have reported a role for NKT-cell-produced IFN-␥ in the induction of NK cell activity (13,19). In the case of LCMV, we have found that the virus-induced NK cell activity is actually normal in an NKT-cell-deficient environment (i.e., CD1d1-deficient mice) (57), and LCMV infection also resulted in the loss of NKT cells in IFN-␥-deficient mice (Table 1).…”

Section: Discussionmentioning

confidence: 91%

Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

Hobbs

Cho

Roberts

et al. 2001

J Virol

106

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Natural killer T (NKT) cells, a unique subpopulation of T cells, coexpress markers also present on NK cellsand recognize the major histocompatibility complex class I-like CD1d1 molecule. We studied the effect of an acute virus infection on NKT cells. Mice were infected with the nonhepatotropic Armstrong strain of lymphocytic choriomeningitis virus (LCMV), and at various times postinfection, mononuclear cells from the liver, peritoneum, and spleen were isolated. It was found that within 2 to 3 days, there was a selective loss of NKT cells from the liver with an apparent rapid recovery within 8 to 14 days. There was no increase in peritoneal or splenic NKT cells, indicating that NKT cells did not traffic to these tissues. This loss of NKT cells was independent of gamma interferon (IFN-␥) and interleukin 12 (IL-12) production, but did occur in mice treated with poly(I-C), a classical inducer of IFN-␣/␤. The reduction in NKT cells was CD28 and fas/fasL independent and occurred via apoptosis. It was not observed in LCMV-infected DNA fragmentation factor 45-deficient mice, and an increase in active caspase 3-specific staining was found in liver NKT cells from LCMV-infected and poly(I-C)-treated mice compared to uninfected wild-type mice. Interestingly, it was also found that liver NKT cells from LCMV-infected mice were themselves infected. These results suggest that the loss of NKT cells following an acute LCMV infection could be due to the induction of IFN-␣/␤ resulting in NKT-cell apoptosis and is important for the host's immune response to LCMV.

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“…NKT cell differentiation towards a Th1 or Th2 direction was often unpredictable [62]. NKT cells are less frequent in humans than they are in mice [2], and high doses of a-GalCer have caused severe liver damage in mice [63]. Furthermore, there is evidence that in the absence of cognate antigen, NKT cells restrain the anti-tumour activity of CpG ODN in mice [64].…”

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confidence: 99%

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

et al. 2005

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Human Va24 + Vb11 + natural killer T cells (NKT cells) are "natural memory" T cells that detect glycolipid antigens such as a-galactosylceramide (a-GalCer) presented on CD1d.In the present study we found that highly purified Va24 + NKT cells lack TLR9 mRNA, and thus are not sensitive towards stimulation with CpG oligodeoxynucleotides (ODN). Within PBMC, however, CpG ODN synergistically activated NKT cells stimulated with their cognate antigen a-GalCer. Depletion of plasmacytoid dendritic cells (PDC) or myeloid dendritic cells (MDC) revealed that both DC subsets were necessary for the synergistic activation of NKT cells by a-GalCer and CpG ODN. While PDC were responsible for the stimulation of NKT cells with CpG ODN, MDC but not PDC presented a-GalCer via CD1d. Partial activation of NKT cells was mediated by PDC-derived IFN-a, whereas full activation of NKT cells as indicated by IFN-c production required cell-tocell contact of PDC and NKT cells in addition to IFN-a; OX40 was involved in this interaction. We conclude that CpG-activated PDC enhance a-GalCer-specific NKT cell activation, and bias activated NKT cells towards a Th1 phenotype. Our results lead to a novel concept of PDC function: to regulate effector activity of antigen-stimulated T cells in a cell contact-dependent manner without the need of simultaneous presentation of the cognate T cell antigen. IntroductionNatural killer T (NKT) cells represent a small subset of non-conventional innate T cells with a restricted TCR repertoire for the recognition of glycolipid antigens presented on CD1d, an MHC class I-like molecule. NKT cells express markers of NK cells and exhibit an activated memory phenotype. Depending on the microenvironment and the type of stimulation, they can release large amounts of both Th1 and Th2 cytokines (especially IL-4 and IFN-c) and show cytotoxic activity in vitro (reviewed in [1][2][3]). In both mice and man NKT cells express a homologous semi-invariant TCR that in humans consists of a Va24 chain preferentially paired with a Vb11 chain [4]. In mice, NKT cells are most frequent in the liver (about 30% of hepatic T cells), bone marrow and thymus (reviewed in [5]). Smaller NKT cell populations are present in spleen and blood (reviewed in [5]). Similar to their murine counterparts, human NKT cells preferen-A. M., S. R. and V. H. equally contributed to this manuscript. tially accumulate in the liver though with a far lower frequency than in mice (4% of hepatic T cells) ([6, 7] and reviewed in [1,5]). Due to the conserved TCR, both mouse and human NKT cells recognise the same specific glycolipid antigen a-galactosylceramide (a-GalCer) when presented by CD1d molecules on antigen-presenting cells (APC) [8][9][10]. Originally isolated from a marine sponge, aGalCer was first described as an agent with strong antimetastatic activity in mice and later found to specifically activate NKT cells in a CD1d-restricted manner [8,11,12]. Glycolipid antigens similar to a-GalCer have been detected in certain bacteria and under some abnormal conditions...

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Activation of hepatic NKT cells and subsequent liver injury following administration of α-galactosylceramide

Cited by 249 publications

References 38 publications

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

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Activation of hepatic NKT cells and subsequent liver injury following administration of α-galactosylceramide

Cited by 249 publications

References 38 publications

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

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Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver