The broad landscape of immune interactions with Staphylococcus aureus: From commensalism to lethal infections

Peres, Adam G.; Madrenas, Joaquı́n

doi:10.1016/j.burns.2012.12.008

Cited by 28 publications

(20 citation statements)

References 80 publications

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“…with PNAG-producing bacteria. Elevated IL-10 production in patients with staphylococcal bacteremia has been associated with an increased mortality rate, likely because of impaired immunity (51). However, as PNAG expression did not impair the clearance of 9142 bacteria while inducing IL-10 production, our results do not suggest a major role for this cytokine in the impairment of host immunity to S. epidermidis.…”

Section: Discussionmentioning

confidence: 46%

Poly- N -Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect

et al. 2016

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Staphylococcus epidermidis is a commensal bacterium of human skin and mucous membranes (1). The ability to establish biofilms on the surfaces of indwelling medical devices is a major virulence mechanism of this bacterium, which is the most commonly isolated etiological agent of nosocomial infections (2). S. epidermidis biofilm formation involves initial cellular adherence to a surface, followed by intercellular aggregation and accumulation in multilayer cell clusters (1). This process is dependent on adhesive extracellular molecules (3) such as poly-N-acetylglucosamine (PNAG). PNAG is a major factor mediating cell-to-cell adhesion in staphylococci (4, 5), and its production depends on genes encoded within the intercellular adhesion (ica) locus (6). The final stage of the biofilm life cycle comprises cell disassembly and subsequent growth in a planktonic mode, a process contributing to S. epidermidis biofilm pathogenesis by disseminating infection (7).S. epidermidis strains with impaired PNAG production display attenuated virulence in foreign body infection models (8, 9), while the production of this polysaccharide conferred a survival advantage on this bacterium infecting the nematode host Caenorhabditis elegans (10). Moreover, ica mutants display growth attenuation when competing in vivo with the corresponding wild-type (WT) strains (11) and commensal ica-negative strains became invasive when transformed with a plasmid containing the ica locus (12). In the clinical setting, the presence of icaA/D genes was associated with therapeutic failure in device-related infections with coagulase-negative staphylococci (13). Despite the observed association of PNAG production with S. epidermidis virulence, it is not entirely clear how this polysaccharide may affect the host immune response. Previous reports have shown that PNAG stimulates the production of proinflammatory mediators (14, 15) but also that it impairs phagocytosis and phagocyte-mediated bacterial killing (16-18). Additionally, little is known about the effects of this polysaccharide on acquired immunity. Here, by using the PNAG-producing S. epidermidis 9142 strain and a PNAG-negative isogenic M10 mutant, we have addressed in the murine model how this polysaccharide affected the host inflammatory response. The results obtained show that mice infected with a PNAG-producing S. epidermidis strain exhibited a more intense inflammatory response than mice infected with an isogenic PNAG-negative mutant. MATERIALS AND METHODSBacteria and growth conditions. Biofilm-forming S. epidermidis strain 9142 (19) and the isogenic PNAG-negative M10 mutant (5) were used. Absence of growth defects in the M10 strain was confirmed, as the two strains had similar generation times, as determined by growing 9142 and M10 bacteria in tryptic soy broth (TSB; Merck, Darmstadt, Germany).

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Section: Discussionmentioning

confidence: 46%

Poly- N -Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect

et al. 2016

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“…Interestingly, recent work in Staphylococcus aureus has also shown that its cell surface contains both proinflammatory and IL-10-inducing immunomodulatory molecules. These peptidoglycan-embedded IL-10-inducing molecules also bind to TLR2 on host antigen-presenting cells, activating the PI3K/Akt pathway, resulting in high levels of production of IL-10, which in turn downregulates the adaptive T cell response (62,63). Thus, the exact receptor(s) by which the SpaCBA pili could mediate cytokine induction remains to be identified.…”

Section: Discussionmentioning

confidence: 99%

Piliation of Lactobacillus rhamnosus GG Promotes Adhesion, Phagocytosis, and Cytokine Modulation in Macrophages

García

Petrova

Claes

et al. 2015

Appl Environ Microbiol

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dRecently, spaCBA-encoded pili on the cell surface of Lactobacillus rhamnosus GG were identified to be key molecules for binding to human intestinal mucus and Caco-2 intestinal epithelial cells. Here, we investigated the role of the SpaCBA pilus of L. rhamnosus GG in the interaction with macrophages in vitro by comparing the wild type with surface mutants. Our results show that SpaCBA pili play a significant role in the capacity for adhesion to macrophages and also promote bacterial uptake by these phagocytic cells. Interestingly, our data suggest that SpaCBA pili also mediate anti-inflammatory effects by induction of interleukin-10 (IL-10) mRNA and reduction of interleukin-6 (IL-6) mRNA in a murine RAW 264.7 macrophage cell line. These pili appear to mediate these effects indirectly by promoting close contact with the macrophages, facilitating the exertion of anti-inflammatory effects by other surface molecules via yet unknown mechanisms. Blockage of complement receptor 3 (CR3), previously identified to be a receptor for streptococcal pili, significantly decreased the uptake of pilus-expressing strains in RAW 264.7 cells, while the expression of IL-10 and IL-6 mRNA by these macrophages was not affected by this blocking. On the other hand, blockage of Toll-like receptor 2 (TLR2) significantly reduced the expression of IL-6 mRNA irrespective of the presence of pili.

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“…By masking FnBP-Amediated activation sCD163 may be able to avoid the adverse effects of uncontrolled overexpression of proinflammatory cytokines and chemokines. In addition, sCD163-mediated inhibition of high IL-10 levels may prevent from staphylococcal immune evasion since high expression of IL-10 is known to allow S. aureus to evade immune responses and to cause septicaemia (Peres and Madrenas, 2013). In conclusion, sCD163 might play a central part in regulating the essential balance of proand anti-inflammatory mechanisms in S. aureus-infected monocytes.…”

Section: Scd163-masking Of Fnbp-a-mediated Inflammatory Activation Ofmentioning

confidence: 98%

Soluble CD163 masks fibronectin-binding protein A-mediated inflammatory activation ofStaphylococcus aureusinfected monocytes

Kneidl¹,

Mysore²,

Geraci

et al. 2013

Cell Microbiol

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SummaryBinding to fibronectin (FN) is a crucial pathogenic factor of Staphylococcus aureus mediated by fibronectin-binding protein A (FnBP-A) and extracellular adherence protein (Eap). Recently, we have shown that binding of soluble CD163 (sCD163) to FN linked to these molecules exhibits anti-microbial effects by enhancing phagocytosis and killing activity of S. aureus-infected monocytes. However, it remained unclear whether sCD163 also influences the monocytic activation status. Using genetically modified staphylococcal strains we now identified FnBP-A, but not Eap, as activator of the inflammatory response of monocytes to infection. FnBP-A-mediated inflammatory activation was masked by sCD163 binding to S. aureus promoting efficient pathogen elimination. Thus, sCD163 protects monocytes from overwhelming activation upon staphylococcal infection by dampening the secretion of pro-inflammatory cytokines TNFα, IL-1β, IL-6 and IL-8 and DAMP molecule MRP8/14. Moreover, sCD163 limited expression of pro-apoptotic transcription factor NR4A1 induced during S. aureus infection and inhibited induction of chemokine CXCL2 promoting survival of staphylococci in vivo. sCD163-mediated effects were not due to general immunosuppression since MAP kinase activation and ROS production were unaltered during infection of monocytes with sCD163-bound bacteria. Thus, sCD163 promotes a specific defence of the immune system against FnBP-A-mediated inflammatory activation enabling successful pathogen elimination, tissue recovery and resolution of inflammation.

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The broad landscape of immune interactions with Staphylococcus aureus: From commensalism to lethal infections

Cited by 28 publications

References 80 publications

Poly- N -Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect

Poly- N -Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect

Piliation of Lactobacillus rhamnosus GG Promotes Adhesion, Phagocytosis, and Cytokine Modulation in Macrophages

Soluble CD163 masks fibronectin-binding protein A-mediated inflammatory activation ofStaphylococcus aureusinfected monocytes

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