A novel sphingomyelinase-like enzyme in Ixodes scapularis tick saliva drives host CD4⁺ T cells to express IL-4

Authors: ALARCON-CHAIDEZ, F.J.; BOPPANA, V.D.; HAGYMASI, A.T.; ADLER, A.J.; WIKEL, S.K.

Source: Parasite Immunology, Volume 31, Number 4, April 2009 , pp. 210-219(10)

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Abstract:

Summary

Tick feeding modulates host immune responses. Tick-induced skewing of host CD4⁺ T cells towards a Th2 cytokine profile facilitates transmission of tick-borne pathogens that would otherwise be neutralized by Th1 cytokines. Tick-derived factors that drive this Th2 response have not previously been characterized. In the current study, we examined an I. scapularis cDNA library prepared at 18-24 h of feeding and identified and expressed a tick gene with homology to Loxosceles spider venom proteins with sphingomyelinase activity. This I. scapularis sphingomyelinase-like (IsSMase) protein is a Mg²⁺-dependent, neutral (pH 7·4) form of sphingomyelinase. Significantly, in an in vivo TCR transgenic adoptive transfer assay IsSMase programmed host CD4⁺ T cells to express the hallmark Th2 effector cytokine IL-4. IsSMase appears to directly programme host CD4 T cell IL-4 expression (as opposed to its metabolic by-products) because induced IL-4 expression was not altered when enzymatic activity was neutralized. TCR transgenic CD4 T cell proliferation (CFSE-dilution) was also significantly increased by IsSMase. Furthermore, a Th2 response is superimposed onto a virally primed Th1 response by IsSMase. Thus, IsSMase is the first identified tick molecule capable of programming host CD4⁺ T cells to express IL-4.

Keywords: BALB/c; CD4; immune modulation; Ixodes scapularis

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-3024.2009.01095.x

Publication date: 2009-04-01