Staphylococcus aureus Skin Colonization Is Enhanced by the Interaction of Neutrophil Extracellular Traps with Keratinocytes

Abstract

Staphylococcus aureus is a facultative pathogen found on skin and nasal surfaces. It is usually absent from the skin of healthy humans but frequently colonizes the skin of patients with atopic dermatitis. Here, we investigate the functional role of neutrophils in the initial steps of S. aureus skin colonization and how skin commensals modulate the S. aureuseinduced recruitment of neutrophils to the skin. Using an epicutaneous mouse skin colonization model, we show that skin inflammation induced by tape-stripping leads to a rapid recruitment of neutrophils, which correlates with enhanced S. aureus skin colonization. Interestingly, the depletion of neutrophils in vivo reduces S. aureus colonization, and in vitro coculture of primary human keratinocytes with neutrophils promotes S. aureus adherence. We demonstrate that the interaction of neutrophil extracellular traps with keratinocytes are responsible for the increased S. aureus skin colonization. Finally, we show that S. epidermidis as part of the skin microbiota can reduce the neutrophil recruitment induced by S. aureus infection. These data suggest that microbiota-mediated skin protection against S. aureus is dampened in an inflammatory environment in which neutrophil extracellular traps released by infiltrating neutrophils unexpectedly contribute to enhanced S. aureus skin colonization.

Glycan-Dependent Corneocyte Adherence of Staphylococcus epidermidis Mediated by the Lectin Subdomain of Aap

“…However, a mechanistic understanding of staphylococcal adherence to the skin surface remains poorly understood, and hence the molecular interactions existent at this bacterial-host interface is an area of significant interest. Adherence of S. aureus to corneocytes in patients with atopic dermatitis (AD) is promoted by the S. aureus surface protein ClfB, in addition to the synthesis of neutrophil extracellular traps (NETs) ( 16 – 18 ). However, AD is an altered skin condition that is complicated by mutations in filaggrin, leading to a loss of functional skin barrier and natural moisturizing factors ( 19 ).…”

eDNA-Mediated Cutaneous Protection Against UVB Damage Conferred by Staphylococcal Epidermal Colonization

“…Intriguingly, the topic of matrix composition and morphological properties of cutaneous staphylococci in a healthy, commensal context compared to very well-described pathological states is rarely mentioned in the literature [6,39]. Most publications refer to diseased skin (namely biopsy sample imaging) [40,41], animal or synthetic skin models [42][43][44], or clinical isolates cultured in vitro under laboratory conditions [45,46]. In these and numerous other disease conditions, there is general agreement among the scientific community that the dominant bacterial morphology is the biofilm form.…”

Net Effects of NETs: New Concepts

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It is challenging to investigate neutrophil extracellular traps (NETs) and bacterial colonization in vivo. Bitschar et al (2020) oppose an existing paradigm regarding neutrophils in host defense and propose that neutrophils increase Staphylococcus aureus skin colonization through NETs, not by trapping microbes but via indirect mechanisms. These results are open to interpretation and should stimulate productive discussions.

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