Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

Abstract

The ectoparasitic mite, Sarcoptes scabiei that burrows in the epidermis of mammalian skin has a long co-evolution with its hosts. Phenotypic studies show that the mites have the ability to modulate cytokine secretion and expression of cell adhesion molecules in cells of the skin and other cells of the innate and adaptive immune systems that may assist the mites to survive in the skin. The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents (HSEs) that changed expression in response to the burrowing of live scabies mites. Overall, of the more than 25,800 genes measured, 189 genes were up-regulated >2-fold in response to scabies mite burrowing while 152 genes were down-regulated to the same degree. HSEs differentially expressed large numbers of genes that were related to host protective responses including those involved in immune response, defense response, cytokine activity, taxis, response to other organisms, and cell adhesion. Genes for the expression of interleukin-1α (IL-1α) precursor, IL-1β, granulocyte/macrophage-colony stimulating factor (GM-CSF) precursor, and G-CSF precursor were up-regulated 2.8- to 7.4-fold, paralleling cytokine secretion profiles. A large number of genes involved in epithelium development and keratinization were also differentially expressed in response to live scabies mites. Thus, these skin cells are directly responding as expected in an inflammatory response to products of the mites and the disruption of the skin’s protective barrier caused by burrowing. This suggests that in vivo the interplay among these skin cells and other cell types, including Langerhans cells, dendritic cells, lymphocytes and endothelial cells, is responsible for depressing the host’s protective response allowing these mites to survive in the skin.

A Proteomic Analysis ofSarcoptes scabiei(Acari: Sarcoptidae)

“…Previous studies have used aqueous extracts of scabies mite whole body homogenates to demonstrate that these mites are the sources of many antigenic and allergenic proteins (Arlian et al 1988a(Arlian et al , 1991(Arlian et al , 1996b(Arlian et al , 2004aMorgan and Arlian 1994;Morgan et al 1997;Arlian and Morgan 2000;Schumann et al 2001) as well as to demonstrate that these mites produce molecules that are able to modulate the immune response of an infested host (Arlian et al 1996c(Arlian et al , 2003(Arlian et al , 2004a(Arlian et al , 2007Elder et al 2006Elder et al , 2009Lalli et al 2004;Bergstrom et al 2009;Arlian 2009, 2010;Mullins et al 2009;Mika et al 2012;Morgan et al 2013;Reynolds et al 2014;Swe and Fischer 2014). The molecules responsible for the observed antigenic and immunomodulatory activities of scabies mite extracts have not been identified.…”

“…It must find a host, penetrate and burrow in the stratum corneum of the epidermis to obtain nutrients and shelter, and the sexes must find each other and mate so that females can produce eggs in order to establish a population in the host all the while avoiding elimination by the host's protective innate and humoral immune responses. Although the mites provoke a defensive response by the host, they are the sources of molecules that down-modulate the initial innate and humoral responses, presumably allowing the mites to survive, reproduce, and establish a population in the host skin (Arlian et al 1996c(Arlian et al , 2003(Arlian et al , 2004b(Arlian et al , 2007Elder et al 2006Elder et al , 2009Lalli et al 2004;Arlian 2009, 2010;Bergstrom et al 2009;Mullins et al 2009;Mika et al 2012;Morgan et al 2013;Reynolds et al 2014;Swe and Fischer 2014).…”

Crusted scabies is associated with increased IL‐17 secretion by skin T cells

“…On the other hand, the local skin environment of crusted scabies may foster the generation of IL-17-secreting T cells; innate immune cells, such as dendritic cells, from crusted scabies pigs may secrete more IL-23 when responding to scabies antigen, or toll-like receptor stimulation when subsequent infections exist. Indeed, microarray studies demonstrate that burrowing mites are capable of inducing IL-23 expression in human skin equivalents (41). Future studies related to this trial will concentrate on further elucidation of factors driving clinical progression to crusted or ordinary scabies, in particular transcriptomic analysis of skin immune responses in early infection.…”

Human demodicosis: revisit and a proposed classification

“…The identification of cathelicidin LL‐37 in inflammatory dermatoses and the differential expression of various cytokines/proteins involved in inflammasome activation shed light on the interaction between skin innate immunity and microbial homoeostasis . Recent observations regarding human scabies infection may help us to understand better how mites can evade immune surveillance or suppress the immune responses . Firstly, all three pathways of the complement system (classical, lectin and alternative) can be inhibited by ‘scabies mite‐inactivated serine protease paralogues’ and ‘serine protease inhibitors’ (serpins).…”