You are here
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.
Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2000 |
Authors | Tuo, W, Palmer, GH, McGuire, TC, Zhu, D, Brown, WC |
Journal | Infect Immun |
Volume | 68 |
Issue | 1 |
Pagination | 270-80 |
Date Published | 2000 Jan |
ISSN | 0019-9567 |
Keywords | Adjuvants, Immunologic, Anaplasma, Animals, Antigens, Bacterial, Bacterial Outer Membrane Proteins, Bacterial Proteins, Base Sequence, Cattle, Cytokines, DNA Primers, Ehrlichia, Gene Expression, Humans, Immunization, Immunoglobulin G, Immunologic Memory, Interferon-gamma, Interleukin-12, Lymphocyte Activation, Neutralization Tests |
Abstract | 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. |
Alternate Journal | Infect. Immun. |
PubMed ID | 10603398 |
PubMed Central ID | PMC97131 |
Grant List | R01-AI30136 / AI / NIAID NIH HHS / United States R01-AI44005 / AI / NIAID NIH HHS / United States |