Mechanism of Bacterial Interference with TLR4 Signaling by Brucella Toll/Interleukin-1 Receptor Domain-containing Protein TcpB

Alaidarous, Mohammed; Ve, Thomas; Casey, Lachlan W.; Valkov, Eugene; Ericsson, Daniel; Ullah, Mujeeb; Schembri, Mark A.; Mansell, Ashley; Sweet, Matthew J.; Kobe, Boštjan

doi:10.1074/jbc.m113.523274

Cited by 66 publications

(82 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such function, found in SARM1 and some plant and bacterial TIRs, is the ability to catalyze NAD degradation (Essuman et al 2018;Horsefield et al 2019;Wan et al 2019). Another function, found in some pathogenic bacteria, is the secretion of cell-permeable TIR proteins to subvert the antibacterial defense mechanisms mediated by host TIRs (Alaidarous et al 2014;Cirl et al 2008). Yet another, more recently evolved function is their participation in cytokine signaling, the emergence of which (and of cytokine signaling in general) coincides with the development of the adaptive immunity in jawed vertebrates (Flajnik and Kasahara 2010;Liongue et al 2016;Rivers-Auty et al 2018), and reflects the increased complexity of associated regulatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

A survey of TIR domain sequence and structure divergence

Toshchakov

Neuwald

2020

Immunogenetics

View full text Add to dashboard Cite

Toll-interleukin-1R resistance (TIR) domains are ubiquitously present in all forms of cellular life. They are most commonly found in signaling proteins, as units responsible for signal-dependent formation of protein complexes that enable amplification and spatial propagation of the signal. A less common function of TIR domains is their ability to catalyze nicotinamide adenine dinucleotide degradation. This survey analyzes 26,414 TIR domains, automatically classified based on group-specific sequence patterns presumably determining biological function, using a statistical approach termed Bayesian partitioning with pattern selection (BPPS). We examine these groups and patterns in the light of available structures and biochemical analyses. Proteins within each of thirteen eukaryotic groups (10 metazoans and 3 plants) typically appear to perform similar functions, whereas proteins within each prokaryotic group typically exhibit diverse domain architectures, suggesting divergent functions. Groups are often uniquely characterized by structural fold variations associated with group-specific sequence patterns and by herein identified sequence motifs defining TIR domain functional divergence. For example, BPPS identifies, in helices C and D of TIRAP and MyD88 orthologs, conserved surface-exposed residues apparently responsible for specificity of TIR domain interactions. In addition, BPPS clarifies the functional significance of the previously described Box 2 and Box 3 motifs, each of which is a part of a larger, group-specific block of conserved, intramolecularly interacting residues.

show abstract

Section: Discussionmentioning

confidence: 99%

A survey of TIR domain sequence and structure divergence

Toshchakov

Neuwald

2020

Immunogenetics

View full text Add to dashboard Cite

show abstract

“…may have evolved a mechanism to subvert innate immunity and IL-1 during infection. Recently, there has been an increased interest in the Toll intracellular domain/IL-1 receptor-containing protein TcpB of Brucella due to its possible interference with Toll-interleukin-1 receptor domaincontaining adapter protein (TIRAP)/Mal and MyD88 signaling through Toll-like and interleukin-1 receptors (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Immune Responses of Bison and Efficacy after Booster Vaccination with Brucella abortus Strain RB51

Olsen¹,

McGill²,

Sacco³

et al. 2015

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

A lthough Brucella abortus can infect other mammalian species, cattle are the preferred host for this species of Brucella. As humans are effectively dead-end hosts, in that brucellosis is essentially not transmitted between people, the maintenance of disease in animal hosts is the source of human infection. For that reason, many industrialized countries have invested heavily in brucellosis control programs in livestock due to public health benefits from the reductions in disease prevalence in animal reservoirs. In the United States, it was estimated in 2000 that approximately 11 billion dollars had been spent in efforts to eradicate brucellosis from cattle. This investment was rewarded in 2008 by the announcement from the U.S. Department of Agriculture that for the first time in the United States, all 50 states were simultaneously free of cattle brucellosis. Despite the eradication of B. abortus from domestic livestock, the persistence of B. abortus infection in freeranging bison and elk at Yellowstone National Park and the surrounding areas remains a concern for the reintroduction of brucellosis to cattle.Previous studies have demonstrated that bison are more susceptible to infection with B. abortus than are cattle, and a single vaccination with B. abortus strain RB51 is effective in reducing the incidence of abortion and infection in bison after experimental challenge (1, 2). In a previous study with a small number of bison, we (3) demonstrated that booster vaccination with RB51 at a 13-month interval increased protection against experimental challenge compared to that provided by a single RB51 vaccination administered during calfhood. In the study reported here, we expand on the previous booster vaccination study with greater experimental units and more extensive bacteriologic and immunologic characterization. MATERIALS AND METHODSB. abortus cultures. For the immunologic assays, RB51 suspensions (1 ϫ 10 12 CFU/ml) were inactivated by gamma irradiation (1.4 ϫ 10 6 rads), washed in 0.15 M sodium chloride (saline), and stored at Ϫ70°C.Animals and inoculation. Eight-to 11-month-old bison heifers were obtained from a brucellosis-free herd. After acclimation, the bison were randomly assigned to receive either saline (control; n ϭ 7) or a single intramuscular vaccination with RB51 (n ϭ 24). Some of the vaccinated bison (n ϭ 16) were randomly selected for booster vaccination with RB51 at 11 months after the initial vaccination.A commercial RB51 vaccine was obtained in lyophilized form (Colorado Serum Company, Denver, CO) and diluted in accordance with the manufacturer's recommendations. All hand inoculations were of 2 ml in volume and administered intramuscularly in the cervical region drained by the superficial cervical lymph node. Following vaccination, the concen-

show abstract

“…Likewise, TcpC can inhibit TLR4 signaling by interacting directly with TRIF and MyD88 [137,138]. A related protein, TcpB from Brucella melitensis, antagonizes TLR4 signaling by interfering with the TLR:MAL interaction [139]; as yet, however, there is no direct evidence to suggest that TcpB also targets the TRIF pathway. Given the essential role of the TRIF pathway in host defense against many bacterial pathogens (see below), as well as the observation that TIR domain-containing proteins are widespread among both pathogenic and nonpathogenic bacteria [140], it is quite likely that other bacterial TIR domain-containing proteins targeting the TRIF signaling axis may be identified.…”

Section: Pathogen-derived Negative Regulatorsmentioning

confidence: 99%

TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target

Ullah

Sweet

Mansell

et al. 2016

Journal of Leukocyte Biology

Self Cite

150

108

View full text Add to dashboard Cite

Toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF)-dependent signaling is required for TLR-mediated production of type-I IFN and several other proinflammatory mediators. Various pathogens target the signaling molecules and transcriptional regulators acting in the TRIF pathway, thus demonstrating the importance of this pathway in host defense. Indeed, the TRIF pathway contributes to control of both viral and bacterial pathogens through promotion of inflammatory mediators and activation of antimicrobial responses. TRIF signaling also has both protective and pathologic roles in several chronic inflammatory disease conditions, as well as an essential function in wound-repair processes. Here, we review our current understanding of the regulatory mechanisms that control TRIF-dependent TLR signaling, the role of the TRIF pathway in different infectious and noninfectious pathologic states, and the potential for manipulating TRIF-dependent TLR signaling for therapeutic benefit.

show abstract

Mechanism of Bacterial Interference with TLR4 Signaling by Brucella Toll/Interleukin-1 Receptor Domain-containing Protein TcpB

Cited by 66 publications

References 63 publications

A survey of TIR domain sequence and structure divergence

A survey of TIR domain sequence and structure divergence

Immune Responses of Bison and Efficacy after Booster Vaccination with Brucella abortus Strain RB51

TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target

Contact Info

Product

Resources

About