Functional assessment of Toll-like receptor 2 and its relevance in patients with Staphylococcus aureus infection of joint prosthesis

El-Helou, Odette; Berbari, Elie F.; Brown, Robert A.; Gralewski, Jonathon H.; Osmon, Douglas R.; Razonable, Raymund R.

doi:10.1016/j.humimm.2010.10.001

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…However, recent reports have determined that one mechanism utilized by biofilms to evade host immunity is by circumventing TLR2 and TLR9 recognition (Figure 1) (Bernthal et al, 2011; Thurlow et al, 2011). This agrees with the finding that patients bearing mutations which inactivate TLR2 have no increased risk of developing post-arthoplasty S. aureus infections (El-Helou et al, 2011). In contrast, the ability of S. aureus biofilms to evade TLR9 recognition differs from P. aeruginosa biofilms, since eDNA has been demonstrated to be a major proinflammatory stimulus during P. aeruginosa biofilm growth (Fuxman Bass et al, 2010).…”

Section: Staphylococcal Biofilms and Toll-like Receptors (Tlrs)supporting

confidence: 90%

Deciphering mechanisms of staphylococcal biofilm evasion of host immunity

Hanke¹,

Kielian²

2012

Front. Cell. Inf. Microbio.

120

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Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using a mouse model of catheter-associated biofilm infection, where S. aureus biofilms led to the accumulation of alternatively activated M2 macrophages that exhibit anti-inflammatory and pro-fibrotic properties. In addition, relatively few neutrophils were recruited into S. aureus biofilms, representing another mechanism that deviates from planktonic infections. However, it is important to recognize the diversity of biofilm infections, in that studies by others have demonstrated the induction of distinct immune responses during staphylococcal biofilm growth in other models, suggesting influences from the local tissue microenvironment. This review will discuss the immune defenses that staphylococcal biofilms evade as well as conceptual issues that remain to be resolved. An improved understanding of why the host immune response is unable to clear biofilm infections could lead to targeted therapies to reverse these defects and expedite biofilm clearance.

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Section: Staphylococcal Biofilms and Toll-like Receptors (Tlrs)supporting

confidence: 90%

Deciphering mechanisms of staphylococcal biofilm evasion of host immunity

Hanke¹,

Kielian²

2012

Front. Cell. Inf. Microbio.

120

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“…TLR2 is located on chromosome 4q32 and it recognizes numerous ligands, most notably peptidoglycan (PGN), which is the major component of the cell wall of Gram-positive bacteria including S. aureus [10]. The most widely characterized single nucleotide polymorphism (SNP) of TLR2 is an amino acid substitution at position 753 from arginine to glutamine.…”

Section: Introductionmentioning

confidence: 99%

Nasopharyngeal Bacterial Colonization and Gene Polymorphisms of Mannose-Binding Lectin and Toll-Like Receptors 2 and 4 in Infants

Vuononvirta

Toivonen

Gröndahl-Yli-Hannuksela

et al. 2011

PLoS ONE

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BackgroundHuman nasopharynx is often colonized by potentially pathogenic bacteria. Gene polymorphisms in mannose-binding lectin (MBL), toll-like receptor (TLR) 2 and TLR4 have been reported. The present study aimed to investigate possible association between nasopharyngeal bacterial colonization and gene polymorphisms of MBL, TLR2 and TLR4 in healthy infants.Methodology/Principal FindingsFrom August 2008 to June 2010, 489 nasopharyngeal swabs and 412 blood samples were taken from 3-month-old healthy Finnish infants. Semi-quantitative culture was performed and pyrosequencing was used for detection of polymorphisms in MBL structural gene at codons 52, 54, and 57, TLR2 Arg753Gln and TLR4 Asp299Gly. Fifty-nine percent of subjects were culture positive for at least one of the four species: 11% for Streptococcus pneumoniae, 23% for Moraxella catarrhalis, 1% for Haemophilus influenzae and 25% for Staphylococcus aureus. Thirty-two percent of subjects had variant types in MBL, 5% had polymorphism of TLR2, and 18% had polymorphism of TLR4. Colonization rates of S. pneumoniae and S. aureus were significantly higher in infants with variant types of MBL than those with wild type (p = .011 and p = .024). Colonization rates of S. aureus and M. catarrhalis were significantly higher in infants with polymorphisms of TLR2 and of TLR4 than those without (p = .027 and p = .002).ConclusionsOur study suggests that there is an association between nasopharyngeal bacterial colonization and genetic variation of MBL, TLR2 and TLR4 in young infants. This finding supports a role for these genetic variations in susceptibility of children to respiratory infections.

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“…Surgical infection is due mainly to Staphylococcus aureus (20,21), a Gram-positive bacterium recognized by TLR2 (22), while a small amount is due to Gram-negative bacteria, bound by TLR4. Accordingly, in infected patients, we observed 87.5% of Grampositive and only 12.5% of Gram-negative infection and, as a consequence, a significant increase of TLR2 but not of TLR4 (Fig.…”

mentioning

confidence: 99%

“…1). TLR2 has been described to be crucial in joint infection (20), contributing to the degenerative process and destructive arthropathy after microbial joint infection (23), indicating that TLR2 expression strictly reflects the progression of the infection in the host. So far, the alteration of TLR2 and TLR4 has been evaluated only at the gene expression level (24,25), while the present work is the first, to our knowledge, which measures the amount of circulating protein, making it suitable for routine clinical diagnosis.…”

mentioning

confidence: 99%