α-Galactosylceramide Promotes Killing of<i>Listeria monocytogenes</i>within the Macrophage Phagosome through Invariant NKT-Cell Activation

Emoto, Masashi; Yoshida, Tomomi; Fukuda, Toshio; Kawamura, Ikuo; Mitsuyama, Masao; Kita, Eisuke; Hurwitz, Robert; Kaufmann, Stefan H. E.; Emoto, Yoshiko

doi:10.1128/iai.01441-09

Cited by 18 publications

(17 citation statements)

References 83 publications

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“…Macrophage influx and activity has been noted to be dependent upon i NKT-cells in diet induced obesity [26], progression of atherosclerotic lesions[27] and models of rheumatoid arthritis[28]. Further, i NKT-cells activate immune cells critical to successful responses to an infection[9,23,29,30] including natural killer cells, macrophages, dendritic cells, T-cells and B-cells. However this interaction appears to be bi-directional wherein macrophages have been noted to modulate i NKT-cell responses.…”

Section: Discussionmentioning

confidence: 99%

“…Emoto et al demonstrated a significant role for iNKT-cells in peritoneal macrophage bactericidal activity, postulating that, following stimulation, i NKT-cells infiltrated the peritoneal cavity[9]. We expand upon their postulation by demonstrating an expansion of the peritoneal i NKT-cell population (7.9% versus 3.2%; p=0.03) in the setting of sepsis, most of which were noted to be activated (73.2% versus 6.9%; p=0.004).…”

Section: Discussionmentioning

confidence: 99%

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Inflammatory Mechanisms in Sepsis

Heffernan¹,

Monaghan²,

Thakkar³

et al. 2013

Shock

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Invariant Natural Killer T-cells (iNKT) cells are emerging as key mediators of innate immune cellular and inflammatory responses to sepsis and peritonitis. iNKT-cells mediate survival following murine septic shock. Macrophages are pivotal to survival following sepsis. iNKT-cells have been shown to modulate various mediators of the innate immune system, including macrophages. Herein we demonstrate sepsis inducing iNKT-cell exodus from the liver appearing in the peritoneal cavity, the source of the sepsis. This migration was affected by Programmed Death Receptor-1(PD-1). PD-1 is an inhibitory immune receptor, reported as ubiquitously expressed at low levels on iNKT-cells. PD-1 has been associated with markers of human critical illness. PD-1 deficient iNKT-cells failed to demonstrate similar migration. To the extent that iNKT-cells affected peritoneal macrophage function we assessed peritoneal macrophages ability to phagocytose bacteria. iNKT−/− mice displayed dysfunctional macrophage phagocytosis and altered peritoneal bacterial load. This dysfunction was reversed when peritoneal macrophages from iNKT−/− mice were co-cultured with wild type iNKT-cells. Together, our results indicate that sepsis induces liver iNKT-cell exodus into the peritoneal cavity mediated by PD-1, and these peritoneal iNKT-cells appear critical to regulation of peritoneal macrophage phagocytic function. iNKT-cells offer therapeutic targets for modulating immune responses and detrimental effects of sepsis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inflammatory Mechanisms in Sepsis

Heffernan¹,

Monaghan²,

Thakkar³

et al. 2013

Shock

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“…In this study, we also found lower levels of MHC class II expression on both DC and macrophages. Since iNKT cells reciprocally activate macrophages and DC upon exposure to pathogens (23,44,45), the loss of MHC class II expression by these APC may have resulted from decreased IFN-␥ expression by iNKT cells. Still, we cannot exclude the possibility that the same factors induced by helminth exposure downregulate both CD1d and MHC class II expression.…”

Section: Mansoni-infected Il-4r␣mentioning

confidence: 99%

Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection

Hsieh

2014

Infect Immun

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“…The cytokines secreted by activated iNKT cells amplify the immune response initiated by these cells through transactivation of other cell types, including conventional CD4 and CD8 T cells, dendritic cells (DCs), NK cells, B cells, regulatory T cells, macrophages, and neutrophils (11), and they influence a broad spectrum of immunological responses, including autoimmunity (13), antimicrobial host responses (14), resistance to tumors (15), and transplantation immunity (16).…”

mentioning

confidence: 99%

Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice

Fang

Dong

et al. 2012

The Journal of Immunology

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This study sought to determine whether invariant NKT (iNKT) cells play an essential role in inflammation-induced preterm delivery. Preterm delivery and fetal death rates were determined in wild-type (WT) C57BL/6 mice and iNKT cell-deficient Jα18−/− mice injected i.p. with LPS. The percentages of decidual immune cells, including activated subsets, and costimulatory molecule expression were analyzed by flow cytometry. Th1 and Th2 cytokine production in the culture supernatants of decidual mononuclear cells was measured by ELISA. To some extent, Jα18−/− mice were resistant to LPS-induced preterm delivery. The proportions of decidual CD3+ and CD49b+ cells were slightly lower in Jα18−/− mice than in WT Jα18+/+ mice, whereas almost no CD3+CD49b+ cells could be found in Jα18-null mice. The percentages of activated decidual DCs, T cells, and NK cells were significantly lower in LPS-treated Jα18−/− mice than in WT mice. The CD40, CD80, and CD86 expression levels on decidual CD11c+ cells from Jα18−/− mice were also significantly lower than in WT mice. Mean concentrations of Th1 cytokines IFN-γ and IL-12p70 in the culture supernatants of decidual mononuclear cells from LPS-treated Jα18−/− mice were apparently lower than those of LPS-induced WT mice. Additionally, the proportions of activated CD11c+ cells, CD3+ cells, and CD49b+ cells in LPS-induced preterm delivery mice were strikingly higher in both WT and null mice when compared with the control PBS group and LPS-injected but normally delivered mice. Our results suggest that iNKT cells may play an essential role in inflammation-induced preterm birth.

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α-Galactosylceramide Promotes Killing ofListeria monocytogeneswithin the Macrophage Phagosome through Invariant NKT-Cell Activation

Cited by 18 publications

References 83 publications

Inflammatory Mechanisms in Sepsis

Inflammatory Mechanisms in Sepsis

Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection

Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice

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