Epidermal keratinocytes initiate wound healing and pro-inflammatory immune responses following percutaneous XXXX .

@entity8236 @entity71406 @entity19 @entity634 @entity635 @entity281 @entity380 @entity22416
UNASSIGNED: Keratinocytes constitute the majority of cells in the skin's epidermis, the first line of defence against percutaneous pathogens. Schistosome larvae (cercariae) actively penetrate the epidermis to establish @entity281 , however the response of keratinocytes to invading cercariae has not been investigated. Here we address the hypothesis that cercariae activate epidermal keratinocytes to promote the development of a pro-inflammatory immune response in the skin. C57BL/6 @entity19 were exposed to @entity380 cercariae via each pinna and non-haematopoietic cells isolated from epidermal tissue were characterised for the presence of different keratinocyte sub-sets at 6, 24 and 96 h p.i. We identified an expansion of epidermal keratinocyte precursors ( @entity8236 (-), CD326(-), @entity22416 (+)) within 24 h of @entity281 relative to na  ve animals. Following @entity281 , cells within the precursor population displayed a more differentiated phenotype (a6integrin(-)) than in uninfected skin. Parallel immunohistochemical analysis of pinnae cryosections showed that this expansion corresponded to an increase in the intensity of @entity22416 staining, specifically in the basal bulge region of hair follicles of infected @entity19 , and a higher frequency of keratinocyte precursor Ki67(+) nuclei in both the hair follicle and interfollicular epidermis. Expression of pro-inflammatory cytokine and stress-associated @entity71406 genes was also transiently upregulated in the epidermal tissue of infected @entity19 . In vitro exposure of keratinocyte precursors isolated from neonatal @entity19 skin to excretory/secretory (E/S) antigens released by penetrating cercaraie elicited @entity634 and @entity635 production, supporting a role for keratinocyte precursors in initiating cutaneous inflammatory immune responses. Together, these observations indicate that @entity380 cercariae and their E/S products act directly upon epidermal keratinocytes, which respond by initiating barrier repair and pro-inflammatory mechanisms similar to those observed in epidermal wound healing.
