Preferential recognition of a microbial metabolite by human V 2V 2 T cells

Puan, Kia Joo; Jin, Chenggang; Wang, Hong; Sarikonda, Ghanashyam; Raker, Amy M.; Lee, Hoi K.; Samuelson, Megan I.; Märker‐Hermann, E.; Paša‐Tolić, Ljiljana; Nieves, Edward; Giner, José‐Luis; Kuzuyama, Tomohisa; Morita, Craig T.

doi:10.1093/intimm/dxm031

Cited by 83 publications

(92 citation statements)

References 111 publications

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“…These T cells recognize nonpeptide lipid antigens, with IPP being one of the primary host molecules. However, activation of host γδ T cells by IPP produced by GAS has largely been discounted because of low concentrations produced in vitro and the discovery that lipid intermediates produced by bacterial pathogens with a nonmevalonic IPP pathway (MEP) are over 10,000-fold more antigenic (31,32).…”

Section: Short-term Changes In the Host Transcriptional Response To Gasmentioning

confidence: 99%

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus

Shea

Virtaneva

Kupko

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Relatively little is understood about the dynamics of global hostpathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host γδ T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our results are unique in providing a comprehensive understanding of the host-pathogen interactome during mucosal infection by a bacterial pathogen.epithelial growth factor receptor | host pathogen | microarray | Streptococcus pyogenes | transcriptome

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Section: Short-term Changes In the Host Transcriptional Response To Gasmentioning

confidence: 99%

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus

Shea

Virtaneva

Kupko

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…gdT cells recognize non-peptide phosphorylated metabolites of isoprenoid biosynthesis, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) being the most potent antigen described. HMBPP is produced by most eubacteria, including Mycobacterium tuberculosis (Mtb) [12]. Prenyl pyrophosphate antigens do not require antigen uptake, processing or intracellular loading for presentation, but are dependent upon cell-to-cell contact.…”

Section: Introductionmentioning

confidence: 99%

CD3 expression distinguishes two γδT cell receptor subsets with different phenotype and effector function in tuberculous pleurisy

Yokobori

Schierloh

Geffner

et al. 2009

Clinical and Experimental Immunology

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SummaryTuberculous pleurisy is a naturally occurring site of Mycobacterium tuberculosis (Mtb) infection. Herein, we describe the expression of activation, natural killer (NK) and cell migration markers, as well as effector functions from gdT cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating gdT from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of gdT cells were differentiated by the CD3/gdT cell receptor (gdTCR) complex. The gdTCR low subset had a higher CD3 to TCR ratio and was enriched in Vd2 + cells, whereas most Vd1 + cells belonged to the gdTCR high subset. In PB from TB, most gdTCR high were CD45RA + CCR7 -and gdTCR low were CD45RA +/-CCR7 + CXCR3 + . In the pleural space the proportion of CD45RA -CCR7 + CXCR3 + cells was higher. Neither spontaneous nor Mtbinduced interferon (IFN)-g production was observed in PB-gdT cells from TB; however, PE-gdT cells showed a strong response. Both PB-and PE-gd T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-gdTCR low cells were the most potent effector cells. Thus, gdT cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As gdT cells produce IFN-g within the pleural space, they would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a T helper type 1 profile.

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“…In healthy individuals, T cells that express the Vd2 chain partnered with Vg9 make up 50-95% of gd T cells in blood (8). Vg9Vd2 T cells are activated by phosphoantigen metabolites of the 2-C-methyl-D-erythritol-4 phosphate isoprenoid biosynthetic pathway [e.g., (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate], which is synthesized by bacterial and protozoan cells but not mammalian cells (9). As a result, Vg9Vd2 T cells were initially postulated to contribute to innate immunity against bacterial infections in humans.…”

mentioning

confidence: 99%

Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

Tsai

Liong

Gunalan

et al. 2015

The Journal of Immunology

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Little is known about the cellular mechanisms of innate immunity against dengue virus (DV) infection. Specifically, the γδ T cell response to DV has not been characterized in detail. In this article, we demonstrate that markers of activation, proliferation, and degranulation are upregulated on γδ T cells in PBMC isolated from individuals with acute dengue fever. Primary γδ T cells responded rapidly in vitro to autologous DV-infected dendritic cells by secreting IFN-γ and upregulating CD107a. The anti-DV IFN-γ response is regulated by type I IFN and IL-18 in a TCR-independent manner, and IFN-γ secreting γδ T cells predominantly expressed IL-18Rα. Antagonizing the ATP-dependent P2X7 receptor pathway of inflammasome activation significantly inhibited the anti-DV IFN-γ response of γδ T cells. Overnight priming with IL-18 produced effector γδ T cells with significantly increased ability to lyse autologous DV-infected dendritic cells. Monocytes were identified as accessory cells that augmented the anti-DV IFN-γ response of γδ T cells. Lack of monocytes in culture is associated with lower IL-18 levels in culture supernatant and diminished production of IFN-γ by γδ T cells, whereas addition of exogenous IL-18 restored the IFN-γ response of γδ T cells in monocyte-depleted cocultures with DV-infected DC. Our results indicate that primary γδ T cells contribute to the immune response during DV infection by providing an early source of IFN-γ, as well as by killing DV-infected cells, and suggest that monocytes participate as accessory cells that sense DV infection and amplify the cellular immune response against this virus in an IL-18–dependent manner.

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Preferential recognition of a microbial metabolite by human V 2V 2 T cells

Cited by 83 publications

References 111 publications

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus

CD3 expression distinguishes two γδT cell receptor subsets with different phenotype and effector function in tuberculous pleurisy

Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

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