A novel sphingomyelinase-like enzyme in Ixodes scapularis tick saliva drives host CD4 T cells to express IL-4.
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 Mg(2+)-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.
Alarcon-Chaidez
F J
FJ
Department of Immunology, University of Connecticut Health Center, Farmington, 06030 USA.
Boppana
V D
VD
Hagymasi
A T
AT
Adler
A J
AJ
Wikel
S K
SK
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000469:parasitology; D003001:Cloning, Molecular; D005260:Female; D006790:Host-Parasite Interactions; D015847:Interleukin-4 / Q000096:biosynthesis*; D018884:Ixodes / Q000201:enzymology* / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis; D012463:Saliva / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D013108:Sphingomyelin Phosphodiesterase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D011994:Recombinant Proteins; D015847:Interleukin-4; D013108:Sphingomyelin Phosphodiesterase