The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens

Lacey, Keenan A.; Geoghegan, Joan A.; McLoughlin, Rachel M.

doi:10.3390/pathogens5010022

Cited by 103 publications

(75 citation statements)

References 108 publications

(189 reference statements)

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“…Similarly, during a murine skin abscess model, IL-22 expression was previously identified to be independent of gd + T cells (34), but it was shown to be protective through the activation of antimicrobial peptide production (38). Inhibition of either IL-17A or IL-22 alone resulted in significantly larger lesion size, providing further evidence that both IL-17A and IL-22 are necessary for local clearance of S. aureus during an S. aureus skin infection (38,39). Consistent with this, we observed a significant increase in the influx of gd + T cells to the site of infection in the absence of IL-10.…”

Section: Discussionmentioning

confidence: 90%

IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

Leech

Lacey

Mulcahy

et al. 2017

The Journal of Immunology

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IL-10 is a potent anti-inflammatory mediator that plays a crucial role in limiting host immunopathology during bacterial infections by controlling effector T cell activation. Staphylococcus aureus has previously been shown to manipulate the IL-10 response as a mechanism of immune evasion during chronic systemic and biofilm models of infection. In the present study, we demonstrate divergent roles for IL-10 depending on the site of infection. During acute systemic S. aureus infection, IL-10 plays an important protective role and is required to prevent bacterial dissemination and host morbidity by controlling effector T cells and the associated downstream hyperactivation of inflammatory phagocytes, which are capable of host tissue damage. CD19+CD11b+CD5+ B1a regulatory cells were shown to rapidly express IL-10 in a TLR2-dependent manner in response to S. aureus, and adoptive transfer of B1a cells was protective during acute systemic infection in IL-10–deficient hosts. In contrast, during localized s.c. infection, IL-10 production plays a detrimental role by facilitating bacterial persistence via the same mechanism of controlling proinflammatory T cell responses. Our findings demonstrate that induction of IL-10 has a major influence on disease outcome during acute S. aureus infection. Too much IL-10 at one end of the scale may suppress otherwise protective T cell responses, thus facilitating persistence of the bacteria, and at the other end, too little IL-10 may tend toward fatal host-mediated pathology through excessive activation of T cells and associated phagocyte-mediated damage.

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Section: Discussionmentioning

confidence: 90%

IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

Leech

Lacey

Mulcahy

et al. 2017

The Journal of Immunology

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“…Keratinocytes recognize the presence of S. aureus using pattern recognition receptors. Toll-like receptor 2 (TLR-2) on keratinocytes recognizes pathogen-associated molecular patterns (PAMPs) including peptidoglycan and lipopeptides [30]. Abu-Humaidan et al [31] have recently found that persistent intracellular S. aureus surviving in epidermal keratinocytes promoted complement activation on the cell surface; this complement activation, in turn, initiated cellular responses that subsequently reduced the intracellular bacterial burden by an extracellular signal-regulated kinase-dependent mechanism.…”

Section: Skin Immune Systemmentioning

confidence: 99%

<b><i>Staphylococcus aureus</i></b> and Host Immunity in Recurrent Furunculosis

Nowicka

Grywalska

2019

Dermatology

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Staphylococcus aureus is one of the severest and most persistent bacterial pathogens. The most frequent S. aureus infections include impetigo, folliculitis, furuncles, furunculosis, abscesses, hidradenitis suppurativa, and mastitis. S. aureus produces a great variety of cellular and extracellular factors responsible for its invasiveness and ability to cause pathological lesions. Their expression depends on the growth phase, environmental factors, and location of the infection. Susceptibility to staphylococcal infections is rooted in multiple mechanisms of host immune responses and reactions to bacterial colonization. Immunological and inflammatory processes of chronic furunculosis are based on the pathogenicity of S. aureus as well as innate and acquired immunity. In-depth knowledge about them may help to discover the whole pathomechanism of the disease and to develop effective therapeutic options. In this review, we focus on the S. aureus-host immune interactions in the pathogenesis of recurrent furunculosis according to the most recent experimental and clinical findings.

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“…For example, despite worldwide efforts, a vaccine for the clinically important Staphylococcus aureus has not made it to the market, yet. Basic research showed the importance of Th1 and Th17 responses in defence against staphylococci [68,69]. While Th17 is prominent in S. aureus clearance from skin and respiratory infections, Th1 responses protect from systemic infection.…”

Section: Multiple Causes May Prevent the Efficacy Of Bacterial Vacmentioning

confidence: 99%

From Immunologically Archaic to Neoteric Glycovaccines

Cavallari

Libero

2017

Vaccines

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Polysaccharides (PS) are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection.

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The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens

Cited by 103 publications

References 108 publications

IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

<b><i>Staphylococcus aureus</i></b> and Host Immunity in Recurrent Furunculosis

From Immunologically Archaic to Neoteric Glycovaccines

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