Journal Article

Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice

Xiong, Xiaolu, Duan, Changsong, Qi, Yong, Gong, Wenping, Wen, Bohai, Jiao, Jun

2014

Overview

•Adr2 is a novel protective antigen of R. rickttsii.•Protection offered by Adr2 is mainly dependent on antigen-specific cell-mediated immune responses.•Adr2 could activate CD4+ and CD8+ T cells to produce great amount of TNF-α and/or IFN-γ as well as elicit rapid increase of specific IgG2a.•Anti-serum against Adr2 could prevent R. rickttsii from invasion of host cells. Rickettsia rickettsii is the pathogen of Rocky Mountain spotted fever (RMSF), a life-threatening tick-transmitted infection. Adr2 was a surface-exposed adhesion protein of R. rickettsii and its immunoprotection against RMSF was investigated in mice. Recombinant Adr2 (rAdr2) was used to immunize C3H/HeN mice, and the rickettsial loads in organs of the mice were detected after challenge with R. rickettsii. The levels of specific antibodies of sera from the immunized mice were determined and the sera from immunized mice were applied to neutralize R. rickettsii. Proliferation and cytokine secretion of CD4+ and CD8+ T cells isolated from R. rickettsii-infected mice were also assayed after rAdr2 stimulation. After R. rickettsii challenge, the rickettsial loads in spleens, livers, and lungs were significantly lower and the impairment degrees of these organs in rAdr2-immunized mice were markedly slighter, compared with those in negative control mice. The ratio of specific IgG2a/IgG1 of rAdr2-immunized mice kept increasing during the immunization. After treatment with rAdr2-immunized sera, the total number of R. rickettsii organisms adhering and invading host cells was significantly lower than that treated with PBS-immunized sera. Interferon-γ secretion by CD4+ or CD8+ T cells and tumor necrosis factor-α secretion by CD4+ T cells from R. rickettsii-infected mice were respectively significantly greater than those from uninfected mice after rAdr2 stimulation. Adr2 is a protective antigen of R. rickettsii. Protection offered by Adr2 is mainly dependent on antigen-specific cell-mediated immune responses, including efficient activity of CD4+ and CD8+ T cells to produce great amount of TNF-α and/or IFN-γ as well as rapid increase of specific IgG2a, which synergistically activate and opsonize host cells to killing intracellular rickettsiae.

• Publisher: Elsevier Ltd,Elsevier
• Subject: adhesion / Adr2 / Allergy and Immunology / Animals / antibodies / Antibodies, Bacterial - blood / antigens / Antigens, Bacterial - immunology / Applied microbiology / Bacterial diseases / Bacterial Load / Bacterial Vaccines - immunology / Bacteriology / Biological and medical sciences / CD4-positive T-lymphocytes / CD4-Positive T-Lymphocytes - immunology / CD8-positive T-lymphocytes / CD8-Positive T-Lymphocytes - immunology / Cell-mediated immunity / Female / Fundamental and applied biological sciences. Psychology / Human bacterial diseases / Immunity, Cellular / Immunity, Humoral / immunization / immunoglobulin G / Immunoglobulin G - blood / Infectious diseases / interferon-gamma / Interferon-gamma - immunology / liver / lungs / Medical sciences / Mice / Mice, Inbred C3H / Microbiology / Miscellaneous / necrosis / neoplasm cells / neutralization / pathogens / Recombinant Proteins - immunology / Rickettsia rickettsii / Rickettsia rickettsii - immunology / Rickettsial diseases / Rocky Mountain spotted fever / Rocky Mountain Spotted Fever - prevention & control / secretion / Serum neutralization / spleen / surface proteins / Tropical bacterial diseases / tumor necrosis factor-alpha / Tumor Necrosis Factor-alpha - immunology / vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)