Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells

Abstract

As a tick feeds, its saliva induces innate and acquired immune responses in the host, including leucocyte infiltration into the bite site. Tick salivary glands produce molecules, however, that counteract many host defences against blood feeding. The effects of salivary-gland extracts (SGE) of Dermacentor andersoni and Ixodes scapularis on the expression of various adhesion molecules [E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)] by the sEND.1 cell line (which is based on cells from the subcutaneous tissue of mice) have now been investigated in vitro. The effects were found to differ with the tick species. The SGE of D. andersoni significantly down-regulated the expression of ICAM-1, whereas a similar extract prepared from I. scapularis significantly reduced the expression of P-selectin and VCAM-1. Tick salivary proteins therefore appear to have direct effects on adhesion-molecule expression, in addition to their previously established roles in down-regulating the pro-inflammatory cytokines that activate endothelial cells. It remains unclear exactly how the reduction of adhesion-molecule expression in the host's endothelial cells benefits the feeding tick but it may alter leucocyte migration to the bite site and/or reduce antigen presentation by the endothelial cells. It may also modulate the interactions between the host's leucocytes and any tick-borne pathogens, during initial infection of the endothelium.

Dermatologic Changes Induced by RepeatedIxodes scapularisBites and Implications for Prevention of Tick-Borne Infection

“…Tick transmitted pathogens have exploited these changes for their own survival. I. scapularis salivary gland extract down-regulates the expression of endothelial cell adhesion molecules P-selectin and vascular cell adhesion molecule-1 that can reduce leukocyte extravasation into dermal tissue (Maxwell et al 2005). These observations help explain the presence of a cell-free zone adjacent to the tick hypostome that we noted after initial tick exposure in mice and human subjects.…”

Prostaglandin E2 Is a Major Inhibitor of Dendritic Cell Maturation and Function in Ixodes scapularis Saliva

“…In fact, tick saliva contains molecules that prevent complement activation (32) and T cell proliferation (13,15,33), and that polarize T cell responses to a Th2 profile (34). Tick saliva also modulates cytokine production by epidermal cells (35) and alters expression of adhesion molecules by skin-derived endothelial cells (36). More recently, a study demonstrated that saliva from R. sanguineus inhibits differentiation, maturation, and cytokine synthesis of bone marrow-derived DCs (20).…”

Transcriptome analysis of the salivary glands of Dermacentor andersoni Stiles (Acari: Ixodidae)

“…A Cu/Zn superoxide dismutase (SOD1) was shown to reduce expression of vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1 in a mouse experimental model of inflammatory bowel disease (IBD) (Segui et al, 2005). It would be tempting to speculate a similar function of the tick protein since ticks are known to modulate the expression of adhesion molecules such as LFA-1 and Mac-1 on neutrophils (Montgomery et al, 2004) and ICAM-1, P-selectin and VCAM-1 on mouse endothelioma cells derived from skin (Maxwell et al, 2005). However, no signal sequence was identified in the tick gene indicating a more likely role in detoxification of metabolic products.…”