A Comprehensive View on the Human Antibody Repertoire Against Staphylococcus aureus Antigens in the General Population

Meyer, Tanja; Michalik, Stephan; Holtfreter, Silva; Weiß, Stefan; Friedrich, Nele; Völzke, Henry; Kocher, Thomas; Köhler, Christian; Schmidt, Frank; Bröker, Barbara M.; Völker, Uwe

doi:10.3389/fimmu.2021.651619

Cited by 27 publications

(37 citation statements)

References 59 publications

(98 reference statements)

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“…21,30,31 Hla promotes blood coagulation via activation of human platelets. This phenomenon is independent of platelet killing, [32][33][34] and consistent with the strong procoagulatory PS exposure on the platelet membrane induced by Hla. In vivo, intravenous injection of Hla in mice induced platelet aggregation and formation of micro-thrombi.…”

Section: Discussionsupporting

confidence: 78%

“…0.56 µM) compared to the Hla concentrations found in patient sera (up to 60 µM ). 34 While platelet activation by various S. aureus proteins like Clumping factor A (ClfA), SdrE, AtlA1, CHIPS, FLIPr, and Eap including Hla is well accepted, the consequences of platelet killing by S. aureus has gained less attention. 3,36 However, killing of platelets might be clinically highly relevant.…”

Section: Discussionmentioning

confidence: 99%

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α-hemolysin ofStaphylococcus aureusimpairs thrombus formation

Jahn

Handtke

Palankar

et al. 2021

Preprint

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Toxins are key virulence determinants of pathogens and can impair the function of host immune cells including platelets. Insights into pathogen toxin interference with platelets will be pivotal to improve treatment of patients with bacterial bloodstream infections. In this study, we deciphered the effects of Staphylococcus aureus toxins α-hemolysin, LukAB, LukDE and LukSF on human platelets and compared the effects with the pore forming toxin pneumolysin of Streptococcus pneumoniae. In contrast to pneumolysin, α-hemolysin initially activates platelets as indicated by CD62P and αIIbβ3 integrin expression, but the resulting pores also induce alterations in the phenotype of platelets and induce apoptosis of platelets. The presence of small amounts of α-hemolysin (0.2 µg/mL) in whole blood abrogates thrombus formation indicating that in systemic infections with S. aureus the stability of formed thrombi is impaired. This might be of high clinical relevance for S. aureus induced endocarditis of the aortic valves. Stabilizing the thrombi by inhibiting α-hemolysin induced impairment of platelets likely reduces the risk for septic (micro-)embolization. However, in contrast to pneumolysin, α-hemolysin induced platelets damage could not be neutralized by intravenous immune globulins. In contrast to α-hemolysin, S. aureus bi-component pore forming leukocidins LukAB, LukED and LukSF do not bind to platelets and had no significant effect on platelet activation and viability.Main point 1: α-hemolysin forms pores in platelets, which first activate but then result in apoptosis and impairs thrombus formation and stabilityMain point 2: Polyvalent immunoglobulins do not neutralize the mode of action of the toxin

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

α-hemolysin ofStaphylococcus aureusimpairs thrombus formation

Jahn

Handtke

Palankar

et al. 2021

Preprint

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“…All humans develop anti-S. aureus antibodies due to life-long exposure to S. aureus through nasal carriage or prior infections. However, the presence of antibodies does not confer protection against future infections and the antibody repertoire against S. aureus, especially in healthy individuals, is highly variable 116 . Elucidating pathogen-specific antibodies to S. aureus and understanding the functional role of the protective versus susceptible nature of an individual's antibody response is essential for the development of successful immunotherapies against S. aureus.…”

Section: Protective Versus Susceptible Immune Responses To S Aureusmentioning

confidence: 99%

Skeletal infections: microbial pathogenesis, immunity and clinical management

et al. 2022

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Osteomyelitis is an infection of bone that can result from contiguous spread from surrounding tissue, direct bone trauma due to surgery or injury, or haematogenous spread from systemic bacteraemia. It remains a significant health-care burden with a prevalence of ~22 cases per 100,000 person-years in the United States, and its incidence has been rising over time, especially in the elderly and individuals with diabetes 1 . Although it is a heterogeneous disease, subset classifications include implant-associated osteomyelitis (including peri-prosthetic joint infection (PJI) and instrumented spinal infections), fracture-related infection, acute haematogenous osteomyelitis, diabetic foot infection, septic arthritis and native spinal osteomyelitis.Crucial to expanding our understanding of osteomyelitis and advancing treatment algorithms has been the application of animal models, which illustrate the interaction between the pathogen and cells of both the immune and skeletal systems in a manner that in vitro models cannot yet replicate. Animal models are available to study virtually all aspects of skeletal infection, and typically involve inoculation of bacteria at the time of implant placement (Fig. 1). They can vary in complexity from simple models where metal implants are placed under the skin (for example, tissue cage 2 ) or into cortical bone (for example, metal wire 3 ) versus more complex models that mimic functional orthopaedic devices 4 . Additionally, approaches have been developed to induce non-implant infections by haematogenous inoculation into the tail vein 5 , direct inoculation into vertebral bodies or intervertebral discs 6 to induce vertebral osteomyelitis, or inoculation into the foot pad of diabetic obese rodents to induce diabetic foot infection 7 .As disease pathogenesis differs across different infection classes, so does microbial aetiology. Many different microorganisms have been implicated in skeletal infection, and the most common, along with their incidence and tropism, are shown in Table 1. In general, Staphylococcus aureus and coagulase-negative staphylococci (CoNS), such as Staphylococcus epidermidis and Staphylococcus lugdunensis, are responsible for up to two-thirds of all skeletal infections, with S. aureus being the most prevalent single pathogen. Additionally, antimicrobial resistance remains a challenge in osteomyelitis treatment with up to 50% of cases of S. aureus osteomyelitis caused by methicillin-resistant S. aureus (MRSA) strains 8 . Other less commonly identified pathogens include Enterococcus spp., Pseudomonas aeruginosa, Escherichia coli and Cutibacterium acnes (Table 1). Most cases of osteomyelitis are monomicrobial; however,

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“…93 S. aureus strains of AE patients but not laboratory strains were reported to accumulate in keratinocytes and induce IL-1alpha via TLR9, 94 further exacerbating the inflammation. It has been shown that different staphylococcal antigens cause individual response on the specific IgG and IgA production, 95 but also interactions between IgE and staphylococcal antigens like SEA, SEB or fibronectin have been reported to play a role in disease development by activating specific IgE-and T cellmediated immune responses. 96,97 In addition, it is also known that S. aureus can evade the T cell-mediated response at different steps and evades immunological memory which may have implications on vaccine development.…”

Section: Immune Systemmentioning

confidence: 99%

A new era of atopic eczema research: Advances and highlights

Hülpüsch

Weins

Traidl‐Hoffmann

et al. 2021

Allergy

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Atopic eczema (AE) or atopic dermatitis (AD) is an inflammatory skin disease with involvement of genetic, immunological and environmental factors which are highly interconnected. 1,2 The heterogenic disease can be separated into different phenotypes and clinical presentations defined by the ethnicity, disease onset, disease severity, chronic vs acute, intrinsic vs extrinsic (IgE level), paediatric vs adult and inflammatory signature. [3][4][5] A common feature of all subtypes is a tremendous psychosocial burden for all patients with AE. 6 Prevalence varies by area and is reported to be 15-20% in children in Europe, persisting in up to 5-10% of adults. [7][8][9] Although severe cases are less abundant than mild or moderate disease pattern, 2% of affected children are severely suffering. 7,9 Therefore, AE remains to be a high and even increasing socio-economic burden in the United States and in Europe, 10,11 whereas slightly decreasing numbers were reported over the last few years in Japan. 12 Children often overcome atopic eczema, but set off on the so-called 'atopic march', that is begin a classic 'allergy career'. Scientifically, AE is a risk factor for the development of allergies. These are primarily type I allergies with clinical features such as hay fever and asthma. Allergies are increasingly becoming a widespread disease. Currently, almost every fourth person in Europe suffers from symptoms such as asthma or hay fever and the associated restrictions in everyday life or at work. For society, the reduced ability to perform at school, university and at work means great socio-economic damage.

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A Comprehensive View on the Human Antibody Repertoire Against Staphylococcus aureus Antigens in the General Population

Cited by 27 publications

References 59 publications

α-hemolysin ofStaphylococcus aureusimpairs thrombus formation

α-hemolysin ofStaphylococcus aureusimpairs thrombus formation

Skeletal infections: microbial pathogenesis, immunity and clinical management

A new era of atopic eczema research: Advances and highlights

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