A Review Stitches Together a Decade of Evidence That Neutrophils Help Staph Colonize Inflamed Skin

The Journal of Investigative Dermatology's September 2026 issue carries a review by Jule Riebelmann and Birgit Schittek that does not report a new experiment. It draws together roughly a decade of separate studies on neutrophils and Staphylococcus aureus, so its value lies in what it synthesizes and where that synthesis still has gaps, not in a novel dataset of its own.

The thread the review builds on starts with a 2020 JID paper (PMID 31857094) that upended a basic assumption. Neutrophil extracellular traps, the web-like DNA structures neutrophils fling out to snare pathogens, were long treated as purely antimicrobial. That paper found NETs interacting with keratinocytes in disrupted skin barrier models helped S. aureus persist rather than clearing it.

A 2023 Cell Reports study (PMID 37733587) filled in the mechanism. NET-keratinocyte contact triggers oxidative stress, keratinocytes release the danger signal HMGB1, and HMGB1 both amplifies further NET formation and suppresses genes that maintain the epidermal barrier, a feed-forward loop identified in cell and mouse models. The same paper reported that serum HMGB1 tracks with disease severity in atopic dermatitis patients, a correlation observed in patient samples rather than a mechanism demonstrated directly in humans.

The strongest causal evidence in this literature is simpler: depleting neutrophils in mice before barrier disruption reduces S. aureus colonization. That is direct causal data, but it comes from tape-stripping mouse models, a standard tool for studying barrier disruption that approximates rather than reproduces chronic human atopic dermatitis skin.

A bioRxiv preprint on Panton-Valentine leukocidin complicates the tidy version of the story. It reports that NETs induced by PVL-producing S. aureus strains lack antimicrobial activity and form readily in patients with recurrent PVL-positive infections. The finding has not cleared peer review, and it signals that the pattern of NETs aiding bacteria may depend on which toxins and strains are involved, so applying it across all clinical S. aureus isolates would overreach the underlying data.

The review's healthy-versus-inflamed framing rests on a separate comparison. S. aureus is essentially absent from healthy human skin, where Staphylococcus epidermidis and other coagulase-negative staphylococci dominate and actively suppress neutrophil recruitment. A 2025 study on AHR-dependent signaling by commensal staphylococci and a 2024 paper showing tissue-resident cells distinguish S. aureus from S. epidermidis via IL-1 beta after barrier disruption both describe healthy skin specifically, evidence that does not automatically transfer to already-inflamed tissue.

Readers tracking this journal should also note a closely related JID piece from earlier in 2025, "The Role of Crosstalk between NETs and Keratinocytes in Skin Immunity," carrying the adjacent identifier pii S0022202X25000120. Whether the September review is a follow-up, a companion piece, or work from an overlapping author group is not stated in the available metadata, and anyone citing both should check for duplicated claims before treating them as independent confirmations.

S. aureus itself is not a passive beneficiary of this loop. The bacterium provokes NET formation through surface protein A and phenol-soluble modulins, then neutralizes the traps it triggered: a secreted nuclease called Nuc degrades NET DNA, and a cell-wall-anchored enzyme, adenosine synthase A, converts the leftover DNA into deoxyadenosine, a compound that kills macrophages and blunts their movement into the site. That two-step sequence, provoke the trap, then repurpose its wreckage, is the concrete mechanism the rest of the review's argument sits on top of.