The role of Toll-like receptors and related receptors of the innate immune system in asthma

Yang, Ian A.; Fong, Kwun M.; Holgate, Stephen T.; Holloway, John W.

doi:10.1097/01.all.0000200503.77295.bb

Cited by 77 publications

(45 citation statements)

References 56 publications

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“…6 Endotoxin or lipopolysaccharide (LPS)-mediated inflammation is believed to be of critical importance in systemic infectious and non-infectious disorders. 7,8 In an animal model, Faas et al 9 demonstrated that infusion of low-dose LPS induces a pre-eclampsia-like syndrome, including hypertension, proteinuria and glomerular endotheliosis. Lipolysaccharide leads to release of pro-inflammatory cytokines through activation of two major pattern recognition receptors present on innate immune cells, including the extracellular Toll-like receptor 2 (TLR2) and TLR4, 10 and the intracellular cryopyrin, a nucleotide-binding oligomerisation domain protein, also known as the caspase-activating recruitment domain.…”

Section: Introductionmentioning

confidence: 99%

Toll‐like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre‐eclampsia

Xie¹,

Hu²,

Turvey

et al. 2009

BJOG

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Objective Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-jB (NF-jB) subunit and interleukin-1b (IL-1b), and inflammatory cytokine profiles in women with preeclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls.Design and method A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1b, NF-jB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-a [TNF-a], interferon-c [IFN-c] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays.Setting A single tertiary maternity hospital in Vancouver, Canada.Population Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia ( ‡34 +0 weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls.Results Women with pre-eclampsia (as a single combined group of early-and late-onset, and particularly in women with earlyonset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-jB subunit, and IL-1b mRNA expression, and TNF-a:IL-10 and IL-6:IL-10 ratios compared with other groups.Conclusions These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.

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Section: Introductionmentioning

confidence: 99%

Toll‐like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre‐eclampsia

Xie¹,

Hu²,

Turvey

et al. 2009

BJOG

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“…This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in T oll-like receptors play an important role in bridging innate and adaptive immune responses in the development of pathogen-associated allergic diseases (1,2). Studies showed that TLR2 agonists protect against allergy and asthma by modulating the immune response Th1/Th2 balance (2)(3)(4).…”

mentioning

confidence: 99%

TLR2 Agonists Enhance CD8+Foxp3+ Regulatory T Cells and Suppress Th2 Immune Responses during Allergen Immunotherapy

Tsai

Yang

Niu

et al. 2010

The Journal of Immunology

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Pam3CSK4, a synthetic TLR2 ligand, has been shown to expand CD4+ regulatory T cells (Treg cells). Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy (IT). This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population. PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times: before IT and 6 mo and 1 y after the maximum-tolerated dose. This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production. Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition. TUNEL revealed that CD8+CD25+ Treg cells, but not CD4+CD25+ Treg cells, directly induced CD4+CD45ROhi+ apoptosis. Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells; therefore, it may be a good adjuvant for the treatment of mite allergies.

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“…Although a strategy to develop vaccines deprived from TLRs has been proposed recently, 23 the activation of TLRs, either directly or through other pattern recognition receptors and signaling machinery, may activate basophils and induce a non IgE-mediated allergic response. 24 A recently published report assessed the role of TLRs in newborns from atopic or asthmatic mothers and showed that TLR2-mediated innate immune responses play a role in increasing the incidence of allergic reactions through the modulation of basophil cytokine secretion and histamine release; furthermore, microbial components released by bacteria, such as formylated peptides, during life, may activate basophils through TLR2 (especially for genetically predisposed infants) to release cytokines associated with an increased incidence of allergic diseases. 25 Activation of non IgE-mediated pathways should elicit CD63 and CD203c upregulation in basophils while skin tests might result negative.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Use of basophil activation test in the investigation of adverse effects to vaccines

Chirumbolo

2011

Human Vaccines

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The role of Toll-like receptors and related receptors of the innate immune system in asthma

Cited by 77 publications

References 56 publications

Toll‐like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre‐eclampsia

Toll‐like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre‐eclampsia

TLR2 Agonists Enhance CD8+Foxp3+ Regulatory T Cells and Suppress Th2 Immune Responses during Allergen Immunotherapy

Use of basophil activation test in the investigation of adverse effects to vaccines

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