RNase 7 Protects Healthy Skin from Staphylococcus aureus Colonization

Persistent Nasal Carriage of Staphylococcus aureus Is Associated with Deficient Induction of Human β-Defensin 3 after Sterile Wounding of Healthy Skin In Vivo

“…This finding is rather unexpected, considering its marked activity against S. aureus, its high concentration found in human skin (7), and its suggested role in preventing S. aureus skin infection (29) and colonization (20). One could argue that RNase 7 is primarily located in superficial nonviable layers of the epidermis devoid of gene transcription and that mRNA levels in lower viable parts of the epidermis, as measured in the presented study, may be a poor reflection of its concentration at the interface of skin and colonizing bacteria.…”

“…Considering the consistency of this finding in both infection and deep wounding and the strength of the association presented here, we believe that this observation represents a true effect and raises questions about the physiological importance and the determinants of this downregulation and thus warrants further investigation. At the same time, lower RNase 7 mRNA levels 72 h after wounding illustrate that the role of this constitutive AMP is characterized by a rapid secretion of preformed RNase 7 protein after superficial injury (6,20) but not by a sustained upregulation of gene expression and support the proposed concept that RNase 7 is an important component of the skin's early and primary response against pathogens (29). This study has particular strengths.…”

“…The only study that quantified RNase 7 protein secretion and S. aureus colonization intensity at the skin surface (6), however, similarly failed to demonstrate an association. Hence, our current knowledge on RNase 7 expression, despite its likely role in preventing colonization of the skin with S. aureus per se (20), is insufficient to support the major importance of this AMP in explaining the population variation of S. aureus nasal colonization. Studies with much larger sample sizes are required to further clarify whether, on average, the 16% lower estimates of constitutive and induced expression of RNase 7 in carriers presented here are a chance finding or indicate a minor contribution of this AMP toward the variation of nasal carriage in the population.…”

“…Together, these observations have led to the general perception of RNase 7 as a constitutively expressed AMP, although studies in cultured keratinocytes after stimulation with heat-inactivated S. aureus and cytokines and one study quantifying RNase 7 protein in hair follicles suggest additional inducibility (7,18). Independent from induced transcription, increased RNase 7 protein concentrations can be detected on the skin surface shortly after superficial skin injury, most likely through the release of preformed AMP (20). In contrast, RNase 7 expression after deep wounding of the skin has not been studied so far.…”

“…A variety of AMPs have been isolated from human skin, but evidence from in vivo studies demonstrating their physiological role in protecting healthy human skin from S. aureus colonization is scarce. One published study showed that AMP-blocking antibodies added onto skin explants lead to enhanced growth of S. aureus (20). While this approach is useful in demonstrating a protective role of AMPs per se, it cannot be used to explore their contribution toward the variation of colonization observed in the population.…”