Enhancement of Innate and Cell-Mediated Immunity by Antimycobacterial Antibodies

• Published in: Infection and Immunity 2005-10, Vol.73 (10), p.6711-6720
• Main Authors: de Vallière, S, Abate, G, Blazevic, A, Heuertz, R. M, Hoft, D. F
• Format: Article
• Language: English
• Subjects: Antibodies, Bacterial - immunology; BCG Vaccine - immunology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins - analysis; Green Fluorescent Proteins - genetics; Humans; Immunity, Cellular; Immunity, Innate; Immunization, Passive; Immunoglobulin G - blood; Immunoglobulin G - immunology; Lipopolysaccharides - immunology; Macrophages - chemistry; Macrophages - microbiology; Microbial Immunity and Vaccines; Microbiology; Monocytes - chemistry; Monocytes - microbiology; Mycobacterium bovis; Mycobacterium bovis - genetics; Mycobacterium bovis - immunology; Neutrophils - chemistry; Neutrophils - microbiology; Phagocytosis - immunology; Tuberculosis - immunology; Tuberculosis - prevention & control
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.73.10.6711-6720.2005

We investigated the ability of human antibodies induced by Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination to protect against mycobacterial infections. Serum samples containing mycobacterium-specific antibodies were obtained from volunteers who had received two intradermal BCG vaccinations 6 months apart. Significant increases in lipoarabinomannan (LAM)-specific immunoglobulin G (IgG) were detected after both the primary and booster vaccinations. Effects of mycobacterium-specific antibodies on surface binding and internalization of BCG by neutrophils and monocytes/macrophages were studied, using green fluorescent protein (gfp)-expressing BCG. Surface-bound gfp-expressing BCG were distinguished from intracellular BCG by surface labeling with LAM-specific monoclonal antibody. Internalization of BCG by phagocytic cells was shown to be significantly enhanced in postvaccination serum samples. Furthermore, the inhibitory effects of neutrophils and monocytes/macrophages on mycobacterial growth were significantly enhanced by BCG-induced antibodies. The growth-inhibiting effects of postvaccination sera were reversed by preabsorption of IgG with Protein G. Finally, the helper effects of antimycobacterial antibodies for the induction of cell-mediated immune responses were investigated. BCG-induced antibodies significantly enhanced proliferation and gamma interferon production in mycobacterium-specific CD4⁺ and CD8⁺ T cells, as well as the proportion of proliferating and degranulating CD8⁺ T cells. We conclude that mycobacterium-specific antibodies are capable of enhancing both innate and cell-mediated immune responses to mycobacteria.