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The function of TLR2 during staphylococcal diseases.

Fournier B - Front Cell Infect Microbiol (2013)

Bottom Line: However, the function of TLRs, and more particularly TLR2, during staphylococcal infections is still debated.In this review we will consider recent findings concerning the staphylococcal ligands sensed by TLR2 and more specifically the role of staphylococcal lipoproteins in TLR2 recognition.A new concept to emerge in recent years is that staphylococcal components must be phagocytosed and digested in the phagosome to be efficiently detected by the TLR2 of professional phagocytes.

View Article: PubMed Central - PubMed

Affiliation: Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine Atlanta, GA, USA. bfourni@emory.edu; bfournier15@yahoo.com

ABSTRACT
Staphylococcus aureus is a versatile pathogen causing a wide range of infections. It has been a major threat both in hospitals and in the community for decades. S. aureus is a pyogenic bacterium that elicits recruitment of polymorphonuclear leukocytes (neutrophils) to the site of infection. Neutrophils are among the first immune cells to migrate to an infection site attracted by chemoattractant gradients, usually initiated in response to inflammation. Neutrophil recruitment to an inflammation and/or infection site is a sophisticated process involving their interaction with endothelial and epithelial cells through adhesion molecules. Phagocytes have various receptors to detect pathogens, and they include Toll-like receptors (TLRs). TLRs have been extensively studied over the last 10 years and it is now established that they are critical during bacterial infections. However, the function of TLRs, and more particularly TLR2, during staphylococcal infections is still debated. In this review we will consider recent findings concerning the staphylococcal ligands sensed by TLR2 and more specifically the role of staphylococcal lipoproteins in TLR2 recognition. A new concept to emerge in recent years is that staphylococcal components must be phagocytosed and digested in the phagosome to be efficiently detected by the TLR2 of professional phagocytes. Neutrophils are an essential part of the immune response to staphylococcal infections, and in the second part of this review we will therefore describe the role of TLR2 in PMN recruitment in response to staphylococcal infections.

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Function of TLR2 during phagocytosis.S. aureus with surface TLR2 ligands (lipoproteins, peptidoglycan, and LTA) is internalized in a TLR2-independent manner and digested in phagosomes. Staphylococcal components are released and stimulate PRRs e.g., TLR2 or Nod2, resulting in phagocyte activation and production of cytokines.
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Figure 2: Function of TLR2 during phagocytosis.S. aureus with surface TLR2 ligands (lipoproteins, peptidoglycan, and LTA) is internalized in a TLR2-independent manner and digested in phagosomes. Staphylococcal components are released and stimulate PRRs e.g., TLR2 or Nod2, resulting in phagocyte activation and production of cytokines.

Mentions: Several articles demonstrate that staphylococcal degradation in the phagosome is required for PAMP release and recognition by PRRs (Kapetanovic et al., 2007; Dietrich et al., 2010; Ip et al., 2010; Shimada et al., 2010; Wolf et al., 2011). Thus, phagocytosis seems to proceed in two steps. First, bacteria are recognized by TLRs at the surface of the phagocytes and this is not dependent on TLR ligands (Figure 2). Indeed, peptidoglycan from S. aureus strains resistant to lysozyme and from wild-type strains release similar amounts of IL-1β and TNFα during the first hour post-infection (Shimada et al., 2010; Wolf et al., 2011), suggesting that peptidoglycan does not require to be degraded at this step. Second, engulfed bacteria are transferred into phagosomes and lysed. During this digestion in the phagosomes, most bacterial cell-wall components and bacterial DNA are released, resulting in materials presented to PRRs (Ip et al., 2010; Wolf et al., 2011). Cytosolic PRRs detecting these structures are either engulfed TLRs such as TLR2, cytosolic TLRs such as TLR9 (a receptor for CpG motifs in DNA), or Nod2 depending on the study (Kapetanovic et al., 2007; Wolf et al., 2011) (Figure 2). Phagocytosis and digestion of pathogens therefore amplify the immune response by presenting motifs recognized by cytosolic PRRs (Wolf et al., 2011). SitC increases intracellular TLR2 and co-localizes with TLR2 (but unlike peptidoglycan, not with Nod2) (Muller et al., 2010; Muller-Anstett et al., 2010). TLR2 and MBL have been reported to co-immunoprecipitate and also co-localize in the phagosome. Importantly, cytochalasin D, a phagocytosis inhibitor, suppresses MBL-induced TNFα, suggesting that internalization is necessary for MLB function (Ip et al., 2008). Thus, internalization seems to be a prerequisite for full S. aureus-induced activation of TLR2, at least in professional phagocyte cells.


The function of TLR2 during staphylococcal diseases.

Fournier B - Front Cell Infect Microbiol (2013)

Function of TLR2 during phagocytosis.S. aureus with surface TLR2 ligands (lipoproteins, peptidoglycan, and LTA) is internalized in a TLR2-independent manner and digested in phagosomes. Staphylococcal components are released and stimulate PRRs e.g., TLR2 or Nod2, resulting in phagocyte activation and production of cytokines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539681&req=5

Figure 2: Function of TLR2 during phagocytosis.S. aureus with surface TLR2 ligands (lipoproteins, peptidoglycan, and LTA) is internalized in a TLR2-independent manner and digested in phagosomes. Staphylococcal components are released and stimulate PRRs e.g., TLR2 or Nod2, resulting in phagocyte activation and production of cytokines.
Mentions: Several articles demonstrate that staphylococcal degradation in the phagosome is required for PAMP release and recognition by PRRs (Kapetanovic et al., 2007; Dietrich et al., 2010; Ip et al., 2010; Shimada et al., 2010; Wolf et al., 2011). Thus, phagocytosis seems to proceed in two steps. First, bacteria are recognized by TLRs at the surface of the phagocytes and this is not dependent on TLR ligands (Figure 2). Indeed, peptidoglycan from S. aureus strains resistant to lysozyme and from wild-type strains release similar amounts of IL-1β and TNFα during the first hour post-infection (Shimada et al., 2010; Wolf et al., 2011), suggesting that peptidoglycan does not require to be degraded at this step. Second, engulfed bacteria are transferred into phagosomes and lysed. During this digestion in the phagosomes, most bacterial cell-wall components and bacterial DNA are released, resulting in materials presented to PRRs (Ip et al., 2010; Wolf et al., 2011). Cytosolic PRRs detecting these structures are either engulfed TLRs such as TLR2, cytosolic TLRs such as TLR9 (a receptor for CpG motifs in DNA), or Nod2 depending on the study (Kapetanovic et al., 2007; Wolf et al., 2011) (Figure 2). Phagocytosis and digestion of pathogens therefore amplify the immune response by presenting motifs recognized by cytosolic PRRs (Wolf et al., 2011). SitC increases intracellular TLR2 and co-localizes with TLR2 (but unlike peptidoglycan, not with Nod2) (Muller et al., 2010; Muller-Anstett et al., 2010). TLR2 and MBL have been reported to co-immunoprecipitate and also co-localize in the phagosome. Importantly, cytochalasin D, a phagocytosis inhibitor, suppresses MBL-induced TNFα, suggesting that internalization is necessary for MLB function (Ip et al., 2008). Thus, internalization seems to be a prerequisite for full S. aureus-induced activation of TLR2, at least in professional phagocyte cells.

Bottom Line: However, the function of TLRs, and more particularly TLR2, during staphylococcal infections is still debated.In this review we will consider recent findings concerning the staphylococcal ligands sensed by TLR2 and more specifically the role of staphylococcal lipoproteins in TLR2 recognition.A new concept to emerge in recent years is that staphylococcal components must be phagocytosed and digested in the phagosome to be efficiently detected by the TLR2 of professional phagocytes.

View Article: PubMed Central - PubMed

Affiliation: Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine Atlanta, GA, USA. bfourni@emory.edu; bfournier15@yahoo.com

ABSTRACT
Staphylococcus aureus is a versatile pathogen causing a wide range of infections. It has been a major threat both in hospitals and in the community for decades. S. aureus is a pyogenic bacterium that elicits recruitment of polymorphonuclear leukocytes (neutrophils) to the site of infection. Neutrophils are among the first immune cells to migrate to an infection site attracted by chemoattractant gradients, usually initiated in response to inflammation. Neutrophil recruitment to an inflammation and/or infection site is a sophisticated process involving their interaction with endothelial and epithelial cells through adhesion molecules. Phagocytes have various receptors to detect pathogens, and they include Toll-like receptors (TLRs). TLRs have been extensively studied over the last 10 years and it is now established that they are critical during bacterial infections. However, the function of TLRs, and more particularly TLR2, during staphylococcal infections is still debated. In this review we will consider recent findings concerning the staphylococcal ligands sensed by TLR2 and more specifically the role of staphylococcal lipoproteins in TLR2 recognition. A new concept to emerge in recent years is that staphylococcal components must be phagocytosed and digested in the phagosome to be efficiently detected by the TLR2 of professional phagocytes. Neutrophils are an essential part of the immune response to staphylococcal infections, and in the second part of this review we will therefore describe the role of TLR2 in PMN recruitment in response to staphylococcal infections.

Show MeSH
Related in: MedlinePlus