TLR-Dependent IL-4 Production by Invariant Vα14+Jα18+ NKT Cells to Initiate Contact Sensitivity In Vivo

Askenase, Philip W.; Itakura, Atsuko; Leite‐de‐Moraes, Maria; Lisbonne, Mariette; Roongapinun, Sukit; Goldstein, Daniel R.; Szczepanik, Marian

doi:10.4049/jimmunol.175.10.6390

Cited by 61 publications

(53 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In yet another mechanism it has been proposed that V␣14i NKT cells express TLR4 and that they can be activated by LPS to produce IL-4 within minutes of stimulation (15). We could not find evidence for either TLR4 or CD14 expression by V␣14i NKT cells.…”

Section: Discussioncontrasting

confidence: 79%

“…The mechanism by which V␣14i NKT cells produce IFN-␥ in response to LPS has not been entirely determined. There have been studies that report TLR expression by these T cells (13)(14)(15), however, there have been others that demonstrate a socalled "indirect" pathway by which V␣14i NKT cells are activated in response to Salmonella or Salmonella LPS (4,16). The indirect pathway postulates that V␣14i NKT cells respond to LPS by integrating two types of signals: one signal is IL-12 produced by activated APCs, which stimulates the IL-12R expressed by V␣14i NKT cells, and the other is the recognition of a relatively weak endogenous GSL Ag presented by CD1d, which stimulates the V␣14i TCR (16).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Invariant NKT Cells Amplify the Innate Immune Response to Lipopolysaccharide

Nagarajan

Kronenberg²

2007

The Journal of Immunology

249

262

View full text Add to dashboard Cite

NKT cells are thought of as a bridge between innate and adaptive immunity. In this study, we demonstrate that mouse NKT cells are activated in response to Escherichia coli LPS, and produce IFN-γ, but not IL-4, although activation through their TCR typically induces both IL-4 and IFN-γ production. IFN-γ production by NKT cells is dependent on LPS-induced IL-12 and IL-18 from APC. LPS induced IFN-γ production by NKT cells does not require CD1d-mediated presentation of an endogenous Ag and exposure to a combination of IL-12 and IL-18 is sufficient to activate them. In mice that are deficient for NKT cells, innate immune cells are activated less efficiently in response to LPS, resulting in the reduced production of TNF and IFN-γ. We propose that in addition to acting as a bridge to adaptive immunity, NKT cells act as an early amplification step in the innate immune response and that the rapid and complete initiation of this innate response depends on the early production of IFN-γ by NKT cells.

show abstract

Section: Discussioncontrasting

confidence: 79%

mentioning

confidence: 99%

Invariant NKT Cells Amplify the Innate Immune Response to Lipopolysaccharide

Nagarajan

Kronenberg²

2007

The Journal of Immunology

249

262

View full text Add to dashboard Cite

show abstract

“…Precedence exists for a link between TLR4 and contact dermatitis in observations that TLR4 can activate iNKT cell and B-1 cell collaboration in the production of Ab responses capable of recruiting Ag-specific T cells (29,30). However, it is unclear from the current investigation why the TLR4 deficiency in C3HeJ did not decrease DNCB-induced contact dermatitis (Fig.…”

Section: Discussionmentioning

confidence: 70%

Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization

Nardo

Braff

Taylor

et al. 2007

The Journal of Immunology

140

117

View full text Add to dashboard Cite

Cathelicidins are antimicrobial peptides of the innate immune system that establish an antimicrobial barrier at epithelial interfaces and have been proposed to have a proinflammatory function. We studied the role of cathelicidin in allergic contact dermatitis, a model requiring dendritic cells of the innate immune response and T cells of the adaptive immune response. Deletion of the murine cathelicidin gene Cnlp enhanced an allergic contact response, whereas local administration of cathelicidin before sensitization inhibited the allergic response. Cathelicidins inhibited TLR4 but not TLR2 mediated induction of dendritic cell maturation and cytokine release, and this inhibition was associated with an alteration of cell membrane function and structure. Further analysis in vivo connected these observations because inhibition of sensitization by exogenous cathelicidin was dependent on the presence of functional TLR4. These observations provide evidence that cathelicidin antimicrobial peptides mediate an anti-inflammatory response in part by their activity at the membrane.

show abstract

“…3c). Given the general effect on all types of T cells, the signal via TLR perhaps represents a previously unrecognised (fourth) signal for T-cell activation, differentiation, survival and memory [7][8][9][10][11][12]. Eur.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, human and murine memory T cells constitutively express surface TLRs and directly recognise TLR agonists [7,9,10]. Moreover, TLR agonists directly promote further TLR expression, survival and the function of NKT and gd T cells [11,12]. Regulatory T cells also possess functional TLR and TLR signals either positively or negatively modulate their suppressive ability [13][14][15].…”

mentioning

confidence: 99%

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex

Komai-Koma¹,

Gilchrist²,

Xu³

2009

Eur J Immunol

View full text Add to dashboard Cite

LPS comprises a major PAMP and is a key target of the immune system during bacterial infection. While LPS can be recognised by innate immune cells via the TLR4 complex, it is unknown whether T lymphocytes, especially CD8 1 T cells are also capable of doing so. We report here that naïve human CD8 1 T cells, after activation by TCR stimulation, express surface TLR4 and CD14. These activated CD8 1 T cells can then secrete high concentrations of IFN-c, granzyme and perforin in response to LPS. These effects can be specifically inhibited using siRNA for TLR4. Furthermore, LPS can synergise with IL-12 to polarise the CD8 1 T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-c but not IL-4, with or without TCR activation. Moreover, CD8 1 CD45RO 1 memory T cells constitutively expressed TLR4 and markedly enhanced IFN-c production when stimulated with LPS. In contrast, activated murine CD8 1 T cells lack TLR4 and CD14 expression and fail to respond to LPS for proliferation and cytokine production. Thus, human but not murine CD8 1 T cells are able to directly recognise bacterial LPS via LPS receptor complex and TLR4 provides a novel signal for the activation of effector and memory human CD8 1 T cells.Key words: CD14 . CD8 1 T cells . Tc1 . LPS . TLR Supporting Information available online IntroductionLPS is an abundant glycolipid in the outer-membrane of Gramnegative bacteria [1][2][3]. It consists of hydrophobic lipid A, the o-polysaccharide chain and a core oligosaccharide [3][4][5]. LPS is perhaps the most well-studied microbial molecule due to its powerful immune activating properties, extremely stable nature and wide distribution in the environment [1][2][3]. It is the key molecule responsible for the bacteria-triggered inflammatory response resulting in organ failure and death [1][2][3]. LPS is also closely associated with pathogenesis of many inflammatory diseases [1][2][3][4]. Despite this, the proinflammatory effects of LPS when harnessed may be beneficial; its powerful effect on both innate and adaptive immunity may provide a new generation of immune adjuvants for vaccine development against infection and cancer [2-4]. Therefore, a clearer understanding of how host recognises LPS is fundamentally important.TLR are a group of evolutionarily developed pathogen-pattern recognition receptors that are widely distributed on immune cells [3,5]. At least ten members of the TLR family in humans have been identified. These recognise different microbial products from bacteria, virus, fungi and parasites [2][3][4]. Host cells recognise LPS via a receptor complex consisting of TLR4, CD14 and MD2 in which LPS only signals through TLR4 and triggers cellular activation and expression of inflammatory genes [2][3][4]. Since TLR was originally identified in Drosophila, which lacks an adaptive immune system, the initial belief was that recognition of pathogen products was a characteristic of innate cells bearing 1564TLR [5,6]. However, the role of T cells bearing TLR in pathogen recognition is less well understood.Growing evide...

show abstract

TLR-Dependent IL-4 Production by Invariant Vα14+Jα18+ NKT Cells to Initiate Contact Sensitivity In Vivo

Cited by 61 publications

References 48 publications

Invariant NKT Cells Amplify the Innate Immune Response to Lipopolysaccharide

Invariant NKT Cells Amplify the Innate Immune Response to Lipopolysaccharide

Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex

Contact Info

Product

Resources

About

TLR-Dependent IL-4 Production by Invariant Vα14+Jα18+ NKT Cells to Initiate Contact Sensitivity In Vivo

Cited by 61 publications

References 48 publications

Invariant NKT Cells Amplify the Innate Immune Response to Lipopolysaccharide

Invariant NKT Cells Amplify the Innate Immune Response to Lipopolysaccharide

Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization

Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex

Contact Info

Product

Resources

About

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex