Toll Receptors: a Central Element in Innate Immune Responses

Vasselon, Thierry; Detmers, Patricia A.

doi:10.1128/iai.70.3.1033-1041.2002

Cited by 194 publications

(133 citation statements)

References 121 publications

(130 reference statements)

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“…TLR4 controls the early events of C. burnetii infection including macrophage phagocytosis, granuloma formation and cytokine production [62]. This receptor is not specific for humans and can also be found in insects [71,174]. Thus, C. burnetii has developed a cell uptake strategy that allows it to invade a broad range of hosts and has developed a unique tactic to multiply in the harsh phagolysosome environment of the cells.…”

Section: Entry and Survival Of C Burnetiimentioning

confidence: 99%

Is Q Fever an emerging or re-emerging zoonosis?

2005

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-Q fever is a zoonotic disease considered as emerging or re-emerging in many countries. It is caused by Coxiella burnetii, a bacterium developing spore-like forms that are highly resistant to the environment. The most common animal reservoirs are livestock and the main source of infection is by inhalation of contaminated aerosols. Although the culture process for Coxiella is laborious, advances on the knowledge of the life cycle of the bacterium have been made. New tools have been developed to (i) improve the diagnosis of Q fever in humans and animals, and especially animal shedders, (ii) perform epidemiological studies, and (iii) prevent the disease through the use of vaccines. This review summarizes the state of the knowledge on the bacteriology and clinical manifestations of Q fever as well as its diagnosis, epidemiology, treatment and prevention in order to understand what factors are responsible for its emergence or re-emergence. Coxiella burnetii / epidemiology / bacteriology / diagnostic / control

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Section: Entry and Survival Of C Burnetiimentioning

confidence: 99%

Is Q Fever an emerging or re-emerging zoonosis?

2005

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“…Toll receptor signaling, which generally signals through NF-B, plays a critical role in inducing an immunological, antimicrobial response (25)(26)(27)(28). Unlike TNF signaling, LPS binds to Toll-like receptor to activate NF-B through TNFRassociated protein-6 (25).…”

Section: Ikk␥c417r Inhibited Lps-induced Ikk Activation and Nf-b Actimentioning

confidence: 99%

“…5A, there were significantly more cell deaths in THP/IKK␥C417R cells than in THP/V cells following TNF stimulation. Several studies reported that LPS also induced monocyte apoptosis through the Fas-associated death domain-containing protein-dependent mechanism (27)(28)(29). Because the percentage of cell death induced by LPS in human THP.1 monocytes was relatively low, the cell death ELISA, which accurately measured DNA fragmentation and histone release from apoptotic cells, was used.…”

Section: Ikk␥c417r Increased Cell Sensitivity To Both Lps and Tnf By mentioning

confidence: 99%

The Zinc Finger Mutation C417R of I-κB Kinase γ Impairs Lipopolysaccharide- and TNF-Mediated NF-κB Activation through Inhibiting Phosphorylation of the I-κB Kinase β Activation Loop

Yang

Yamashita

Tang³

et al. 2004

The Journal of Immunology

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The activation of the I-κB kinase (IKK) complex by TNF or LPS stimulates phosphorylation and degradation of I-κBα, leading to the nuclear translocation of NF-κB. The IKK complex is mainly composed of two catalytic subunits, IKKα and IKKβ, and a chaperon subunit IKKγ. Although IKKγ does not have catalytic activity, it is essential for IKK activation induced by multiple stimuli. Importantly, the key residue cysteine 417 at the zinc finger domain of IKKγ has been found to be mutated to arginine (IKKγC417R) in a human genetic disorder called the anhydrotic ectodermal dysplasia with immunodeficiency. To understand the underlying mechanisms of immunodeficiency, we examined whether the IKKγC417R mutant modified IKK activation and NF-κB transcription stimulated by LPS or TNF in human monocytes. We found that overexpression of IKKγC417R severely impaired LPS- and TNF-induced I-κBα phosphorylation and degradation in a dominant-negative fashion. Also, LPS- and TNF-induced NF-κB transcription was inhibited by IKKγC417R. The reconstitution of IKKγ, but not IKKγC417R, in IKKγ-deficient cells restored NF-κB signaling, indicating the zinc finger structure of IKKγ plays a key role in IKK activation. Moreover, C417R mutation in IKKγ abolished both LPS- and TNF-induced phosphorylation of the activation loop of IKKβ. Collectively, our results indicated that the zinc finger structure of IKKγ plays a key role in LPS- and TNF-induced NF-κB activation. The anhydrotic ectodermal dysplasia with immunodeficiency patients’ immunodeficiency may be associated with NF-κB defect in response to bacterial stimulation.

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“…The mammalian innate immune system provides host defense against a variety of pathogens without requiring prior exposure (5,6), and genes modulating innate immunity have often been considered candidate loci for improving host resistance to disease in agricultural species. The recently evolved field of innate immunity was originally catalyzed by the discovery that TOLL, a Drosophila protein governing developmental polarity, was also required for an effective antifungal immune response in adult Drosophila (7)(8)(9)(10).…”

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confidence: 99%

Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle

Seabury

Seabury²,

Decker³

et al. 2009

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

100

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The Toll-like receptor (TLR) and peptidoglycan recognition protein 1 (PGLYRP1) genes play key roles in the innate immune systems of mammals. While the TLRs recognize a variety of invading pathogens and induce innate immune responses, PGLYRP1 is directly microbicidal. We used custom allele-specific assays to genotype and validate 220 diallelic variants, including 54 nonsynonymous SNPs in 11 bovine innate immune genes (TLR1-TLR10, PGLYRP1) for 37 cattle breeds. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and we were unable to differentiate between the specialized B. t. taurus beef and dairy breeds, despite an average polymorphism density of one locus per 219 bp. Ninety-nine tagSNPs and one tag insertion-deletion polymorphism were sufficient to predict 100% of the variation at all 11 innate immune loci in both subspecies and their hybrids, whereas 58 tagSNPs captured 100% of the variation at 172 loci in B. t. taurus. PolyPhen and SIFT analyses of nonsynonymous SNPs encoding amino acid replacements indicated that the majority of these substitutions were benign, but up to 31% were expected to potentially impact protein function. Several diversitybased tests provided support for strong purifying selection acting on TLR10 in B. t. taurus cattle. These results will broadly impact efforts related to bovine translational genomics.peptidoglycan recognition protein | bovine translational genomics | bovine Toll-like receptors | single nucleotide polymorphism

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Toll Receptors: a Central Element in Innate Immune Responses

Cited by 194 publications

References 121 publications

Is Q Fever an emerging or re-emerging zoonosis?

Is Q Fever an emerging or re-emerging zoonosis?

The Zinc Finger Mutation C417R of I-κB Kinase γ Impairs Lipopolysaccharide- and TNF-Mediated NF-κB Activation through Inhibiting Phosphorylation of the I-κB Kinase β Activation Loop

Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle

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