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Infection and Immunity, January 2000, p. 270-280, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interleukin-12 as an Adjuvant Promotes Immunoglobulin G and Type 1 Cytokine Recall Responses to Major Surface Protein 2 of the Ehrlichial Pathogen Anaplasma marginale

Wenbin Tuo,dagger Guy H. Palmer, Travis C. McGuire, Daming Zhu, and Wendy C. Brown*

Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040

Received 25 June 1999/Returned for modification 5 August 1999/Accepted 11 October 1999

Anaplasma marginale is a tick-transmitted pathogen of cattle closely related to the human ehrlichiae, Ehrlichia chaffeensis and the agent of human granulocytic ehrlichiosis (HGE). These pathogens have in common a structurally conserved outer membrane protein (OMP) designated the major surface protein 2 (MSP-2) in A. marginale and HGE and OMP-1 in E. chaffeensis. Protective immunity against ehrlichial pathogens is believed to require induction of gamma interferon (IFN-gamma ) and opsonizing immunoglobulin (Ig) subclasses directed against OMP epitopes that, in concert, activate macrophages for phagocytosis and killing. Because interleukin-12 (IL-12) acts as an adjuvant for protein immunization to induce IFN-gamma and protective immunity against intracellular pathogens, we hypothesized that as an adjuvant with MSP-2, IL-12 would augment type 1 recall responses to A. marginale. IL-12 was coadsorbed with MSP-2 to alum and shown to significantly enhance IFN-gamma production by lymph node cells (LNC) and LNC-derived CD4+ T-cell lines from immunized calves following recall stimulation with A. marginale. LNC proliferation and IL-2 production were also enhanced in IL-12-treated calves. Elevated recall proliferative responses by peripheral blood mononuclear cells were still evident 9 months after immunization. Serum IgG levels were consistently increased in IL-12 immunized calves, predominantly due to higher IgG1 responses. The results support the use of IL-12 coadsorbed with OMP of ehrlichial pathogens in alum to amplify both antibody and type-1 cytokine responses important for protective immunity.

* Corresponding author. Mailing address: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040. Phone: (509) 335-6067. Fax: (509) 335-8529. E-mail: wbrown{at}vetmed.wsu.edu.

dagger Present address: Animal Disease Research Unit, ARS/USDA, Washington State University, Pullman, WA 99164-7030.

Infection and Immunity, January 2000, p. 270-280, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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