Wound healing in skin promoted by inoculation with Pseudomonas aeruginosaPAO1: The critical role of tumor necrosis factor‐α secreted from infiltrating neutrophils

Abstract

Wound healing is promoted by the presence of replicating microorganisms adhering to the wounded tissue, but the precise mechanism is not fully understood. In the present study, using a rat model with full-thickness dermal wounds, we examined the effect of Pseudomonas aeruginosa inoculation on wound healing and the role of neutrophils infiltrating the wound site. Within 3 days, inoculation with this bacterium had accelerated re-epithelialization, epidermal cell proliferation, and neo-vascularization, as well as the local infiltration of neutrophils, which reached a peak at 24 hours. Tumor necrosis factor (TNF)-α was detected in the wound tissues on the mRNA and protein levels within 24 hours. Flow cytometry and immunohistochemical analyses detected higher levels of TNF-α in the infiltrating neutrophils in rats inoculated with P. aeruginosa than in uninoculated rats. Neutropenic rats treated with anti-neutrophil mAb or cyclophosphamide exhibited significant attenuation in re-epithelialization, epidermal cell proliferation, neo-vascularization, and TNF-α synthesis compared with control; administration of TNF-α reversed these attenuations. These wound-healing responses were decelerated in rats treated with anti-TNF-α mAb, as was the infiltration of neutrophils. These results indicate that inoculation with P. aeruginosa promotes wound healing by inducing the infiltration of neutrophils, which play a critical role as a major source of TNF-α.

Ciprofloxacin-Loaded Keratin Hydrogels PreventPseudomonas aeruginosaInfection and Support Healing in a Porcine Full-Thickness Excisional Wound

“…37 Conversely, others have shown that inoculating rodent wounds with P. aeruginosa strain PA01 at concentrations > 10 7 cfu per wound accelerates reepithelialization by triggering an immediate neutrophil response and subsequent TNF-a production. 38 The primary objective of this study was to assess the ability of keratose hydrogels with and without ciprofloxacin to inhibit infection in a clinically relevant model. Further, we wanted to ensure that locally delivered keratin-ciprofloxacin formulations did not cause any healing irregularities, as seen with therapies such as silver creams.…”

Pseudomonas aeruginosa flagellum is critical for invasion, cutaneous persistence and induction of inflammatory response of skin epidermis

“…IL-32 is a cytokine involved in the induction of IL-6, TNFα and chemokines [31,32]. TNFα, IL-6, IL-23 and TSLP have been described as mediators involved in host defense against P. aeruginosa [18,26,33–35]. Together with cytokines, chemokines contribute induction and maintenance of inflammation by regulating the composition of the cellular infiltrates in the skin.…”

Dynamic Role of Host Stress Responses in Modulating the Cutaneous Microbiome: Implications for Wound Healing and Infection

“…35 In parallel, diabetic and chronic wounds exhibit a similar predominance of S. aureus in the epidermal microbiome; these changes are associated with excess inflammation and delayed wound healing responses. 19,[36][37][38] Further, we recently determined that significant changes in the human bacterial microbiome occur in both the burn margin as well as distal, uninjured skin sites after burn injury, which is characterized by an increase in the abundance of Gram-negative bacteria. * Thus, the presence of primary disease combined with acute skin injury has the potential to elicit acute or prolonged stress responses, which likely influence wound repair processes by modulating both host innate immune response and the microbiome.…”

“…Table 2 illustrates the interactions of select members of the microbiome and TLRs. 4,[14][15][16]19,35,37,38,47,50,51 The continuous research in the field of microbial endocrinology will hopefully unify clinicians and basic scientists in an effort to expand this unexplored area in the context of wound healing and infection as well as elucidate how host stress mediators influence bacterial antimicrobial mechanisms and the host's response to commensal versus pathogenic bacteria.…”