Cytokine Production by Lymph Node Cells from Mice Infested with Ixodes ricinus Ticks and the Effect of Tick Salivary Gland Extracts on IL‐2 Production

Abstract

In BALB/c mice repeatedly infested with nymphal Ixodes ricinus ticks, lymphocytes from axillary and brachial lymph nodes which drain the tick attachment site produced significant levels of IL-2, TNF-alpha and GM-CSF when stimulated in vitro with Con A or anti-CD3 antibodies. Cytokine production by cells from lymph nodes of the opposite flank was equivalent to that of cells from uninfested mice. Nine days after the first infestation and IL-2, GM-CSF were produced primarily by the CD4+ T cells, while some other cell types contributed also to the TNF-alpha production. In mice repeatedly infested, a gradual increase of lymph node cell production of IL-2 was observed. The IL-2 levels regularly increased from the first to the third infestation compared to TNF-alpha levels which gradually decreased. The in vitro production of GM-CSF was not affected by successive infestations. Spleen lymphocytes from naive mice produced higher levels of IL-2 than lymphocytes from axillary and brachial lymph nodes. Both tick salivary gland extracts and D-mannose inhibited IL-2 production by these lymphocytes.

Identification of an IL-2 Binding Protein in the Saliva of the Lyme Disease Vector Tick, Ixodes scapularis

“…Furthermore, it was demonstrated with ELISA and bioassays that treatment of spleen cells (SC) with tick saliva resulted in a decrease in IL-2 production (24). This observation has also been made by others working with different tick species (20,23,27,30).…”

“…This phenomenon has been demonstrated with mouse T cells by using Con A (16,(23)(24)(25)(26)(27)(28), PHA (24), and anti-CD3 (20). This effect has also been demonstrated on bovine lymphocytes with Con A stimulation (29,30).…”

“…Although a large body of evidence supports the existence of nonspecific T cell inhibitory activities in the saliva of several species of ixodid ticks (16,20,(23)(24)(25)(26)(27)(28)(29), with one exception (29), definitive experiments aimed at elucidating the mechanism of T cell proliferation inhibitory factors have been lacking. Toward this end, Urioste et al (24) demonstrated that the major T cell inhibitory activity in I. scapularis saliva is proteinaceous due to its inactivation by trypsin treatment.…”

“…This body of observations makes it clear that ticks have evolved a remarkable array of biochemical weapons to keep the host at bay and assure their own success as a species. The protective functions of vector saliva may also have the important, though presumably inadvertent, effect of potentiating the transmission of various pathogens to hosts through the alteration of the immunologic microenvironment at the feeding site (1,2) or the lymph nodes draining the site of attachment (17)(18)(19)(20).…”

Isolation of Ixodes ricinus salivary gland mRNA encoding factors induced during blood feeding.

“…[12][13][14] Indeed, the alternative pathway of the complement is inhibited 15,16 and the activity of lymphoid cells is modified. [17][18][19][20][21][22][23] For tick infestation, interleukin (IL)-4, IL-5, and IL-10 induction and IL-2 and interferon gamma inhibition [24][25][26] are observed, indicating a polarized Th2 host immune response. 13 It has also been observed that during the bloodmeal, new mRNAs are induced in the salivary glands, leading to the synthesis of a wide range of new proteins.…”