Cutting Edge: TLR2 Directly Triggers Th1 Effector Functions

Imanishi, Takayuki; Hara, Hiromitsu; Suzuki, Shinobu; Suzuki, Nobutaka; Akira, Shizuo; Saito, Takashi

doi:10.4049/jimmunol.178.11.6715

Cited by 181 publications

(186 citation statements)

References 24 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…The present studies suggest that TLR4 signals directly drive Tc1 development in the presence of TCR or IL-12 signals. While the mechanism is still unclear and currently under investigation, this is in agreement with the previous findings that BLP preferentially promotes human and murine Th1 but not Th2 cell differentiation [7,8] and that TLR agonists selectively stimulate IFN-g but not IL-4 production by human gd T cells [9,10,12]. Our results therefore support current evidence and suggest the existence of a novel type I T-cell development pathway by directly recognising PAMP via TLRs on T cells.…”

supporting

confidence: 92%

“…We reported for the first time that human CD4 1 T cells express functional TLR2 and that TLR2 signals directly promote T-cell function [7]. This was subsequently confirmed in mice [8]. Furthermore, human and murine memory T cells constitutively express surface TLRs and directly recognise TLR agonists [7,9,10].…”

mentioning

confidence: 76%

“…Growing evidence suggests that T cells participate in immune microbial surveillance [7][8][9][10]. We reported for the first time that human CD4 1 T cells express functional TLR2 and that TLR2 signals directly promote T-cell function [7].…”

Section: Introductionmentioning

confidence: 91%

“…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.…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

supporting

confidence: 92%

mentioning

confidence: 76%

Section: Introductionmentioning

confidence: 91%

mentioning

confidence: 99%

See 2 more Smart Citations

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

show abstract

“…In addition, it has been recently shown that TLR2 mediates Th1 responses via direct stimulation of Th1 cells and via IL-12 production by APCs, and that TLR2-mediated INF-γ production is crucial for protective immunity against several infectious pathogens [71]. As Nme PorB has been shown to activate immune cells via a TLR2-mediated mechanism [31], we have examined whether the immune adjuvant effect of Nlac PorB might have a similar mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Liu

Wetzler

Massi

2008

Vaccine

View full text Add to dashboard Cite

Porins from pathogenic Neisseriae are among several bacterial products with immune adjuvant activity. N. meningitidis (Nme) PorB, has been shown to induce immune cells activation in a TLR2-dependent manner and acts as a vaccine immune adjuvant. The PorB porin from Neisseria lactamica (Nlac), a common nasopharyngeal commensal shares significant structural and functional similarities with Nme PorB. In this work we ask whether the immune adjuvant ability of porins from pathogenic Neisserial strains is a characteristic shared with porins from non-pathogenic Neisserial species or whether it is unique for bacterial products derived from microorganisms capable of inducing inflammation and disease. We evaluate the potential immune adjuvant effect of Nlac PorB in mice using ovalbumin (OVA) as a prototype antigen. Immunization with Nlac PorB/OVA induced high OVA-specific IgG and IgM titers compared to OVA alone, similar to other adjuvants such as Nme PorB and alum. High titers of IgG1 and IgG2b were detected as well as production of IL-4, IL-10, IL-12 and INF-γ in response to Nlac PorB, consistent with induction of both a Th1-type and a Th2-type immune response. OVA-specific proliferation was also determined in splenocytes from Nlac PorB/OVA immunized mice. In addition, B cell activation in vitro and cytokine production in response to Nlac PorB was found to be mediated by TLR2, in a similar manner to Nme PorB.

show abstract

Modern Subunit Vaccines: Development, Components, and Research Opportunities

2013

View full text Add to dashboard Cite

Traditional vaccines, based on the administration of killed or attenuated microorganisms, have proven to be among the most effective methods for disease prevention. Safety issues related to administering these complex mixtures, however, prevent their universal application. Through identification of the microbial components responsible for protective immunity, vaccine formulations can be simplified, enabling molecular-level vaccine characterization, improved safety profiles, prospects to develop new high-priority vaccines (e.g. for HIV, tuberculosis, and malaria), and the opportunity for extensive vaccine component optimization. This subunit approach, however, comes at the expense of decreased immunity, requiring the addition of immunostimulatory agents (adjuvants). As few adjuvants are currently used in licensed vaccines, adjuvant development represents an exciting area for medicinal chemists to play a role in the future of vaccine development. In addition, immune responses can be further customized though optimization of delivery systems, tuning the size of particulate vaccines, targeting specific cells of the immune system (e.g. dendritic cells), and adding components to aid vaccine efficacy in whole immunized populations (e.g. promiscuous T-helper epitopes). Herein we review the current state of the art and future direction in subunit vaccine development, with a focus on the described components and their potential to steer the immune response toward a desired response.

show abstract

Cutting Edge: TLR2 Directly Triggers Th1 Effector Functions

Cited by 181 publications

References 24 publications

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

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

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Modern Subunit Vaccines: Development, Components, and Research Opportunities

Contact Info

Product

Resources

About

Cutting Edge: TLR2 Directly Triggers Th1 Effector Functions

Cited by 181 publications

References 24 publications

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

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

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Modern Subunit Vaccines: Development, Components, and Research Opportunities

Contact Info

Product

Resources

About

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

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