Tuberculosis Research Today is a free monthly online journal that collates and summarizes the latest research about Tuberculosis, including details on symptoms, causes, treatment, pulmonary, mycobacterium. | ||||||||
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Adjuvant modulation of the cytokine balance in Mycobacterium tuberculosis subunit vaccines; immunity, pathology and protection.Agger EM, Cassidy JP, Brady J, Korsholm KS, Vingsbo-Lundberg C, Andersen P Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. eag@ssi.dk It is known that protection against tuberculosis is mediated primarily by T helper type 1 (Th1) cells but the influence of the Th1/Th2 balance of a vaccination response on the subsequent protection and pathology during infection has not been studied in detail. We designed a panel of Ag85B-ESAT-6 subunit vaccines based on adjuvants with different Th1/Th2-promoting activities and studied cellular responses, bacterial replication and pathology in the lungs of mice infected with Mycobacterium tuberculosis. All vaccines induced cell-mediated and humoral responses but with markedly different interferon-gamma : interleukin-5 (IFN-gamma : IL-5) and immunoglobulin G1 (IgG1) : IgG2 ratios. The vaccines promoted different levels of control of bacterial replication with the most efficient protection being exerted by cationic liposomes containing monophosphoryl lipid A and low to completely absent immunity with conventional aluminium. The level of protection correlated with the amount of IFN-gamma produced in response to the vaccine whereas there was no inverse correlation with the level of IL-5. Characterizing a protective response was an accelerated recruitment of IL-17 and IFN-gamma-producing lymphocytes resulting in the early formation of granulomas containing clustered inducible nitric oxide synthase-activated macrophages. In comparison, non-protected mice exhibited a different inflammatory infiltrate rich in neutrophil granulocytes. This study indicates that the adjuvant component of a tuberculosis vaccine may be crucial in determining the kinetics by which effective granulomas, pivotal in controlling bacterial growth, are formed. Published 20 May 2008 in Immunology, 124(2): 175-85.
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