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Infection and Immunity, June 2009, p. 2320-2329, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01507-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Inhibition of Neutrophil Function by Two Tick Salivary Proteins{triangledown}

Xiuyang Guo,1 Carmen J. Booth,2 Michael A. Paley,1 Xiaomei Wang,1 Kathleen DePonte,1 Erol Fikrig,1 Sukanya Narasimhan,1 and Ruth R. Montgomery1*

Department of Internal Medicine,1 Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 065202

Received 10 December 2008/ Returned for modification 16 January 2009/ Accepted 21 March 2009

The saliva of hematophagous arthropods contains potent anti-inflammatory and antihemostatic activities that promote acquisition of the blood meal and enhance infection with pathogens. We have shown that polymorphonuclear leukocytes (PMN) treated with the saliva of the tick Ixodes scapularis have reduced expression of β2 integrins, impaired PMN adherence, and reduced killing of Borrelia burgdorferi, the causative agent of Lyme disease. Here we describe two Ixodes proteins that are induced upon tick feeding and expressed predominantly in the salivary glands. Using saliva harvested from ticks with reduced levels of ISL 929 and ISL 1373 through targeted RNA interference knockdown, as well as purified recombinant proteins, we show the effects of these proteins on downregulation of PMN integrins and inhibition of the production of O2– by PMN in vitro. Mice immunized with ISL 929/1373 had increased numbers of PMN at the site of tick attachment and a lower spirochete burden in the skin and joints 21 days after infection compared to control-immunized animals. Our results suggest that ISL 929 and ISL 1373 contribute to the inhibition of PMN functions shown previously with tick saliva and support important roles for these inhibitory proteins in the modulation of PMN function in vivo.

* Corresponding author. Mailing address: Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8031. Phone: (203) 785-7039. Fax: (203) 785-7053. E-mail: ruth.montgomery{at}yale.edu

{triangledown} Published ahead of print on 30 March 2009.

Editor: J. B. Bliska

Infection and Immunity, June 2009, p. 2320-2329, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01507-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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