M. tuberculosis: immunology and vaccination

Abstract

Tuberculosis is increasing. Current treatment regimens require at least 6 months, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and "directly observed therapy short course" (DOTS) is having less impact than expected. This worrying situation is aggravated by coinfection with human immunodeficiency virus (HIV), and by the increase in drug-resistant strains.We need new insights that lead to more rapid therapies and immunotherapies, and more reliable vaccines.Recent insights have come from: understanding of the relationship between Mycobacterium tuberculosis and macrophages; the multiple T cell types that recognise mycobacterial peptides, lipids and glycolipids; the critical role of interferon-c (IFNc) and interleukin-12 (IL-12) in human mycobacterial infection revealed by genetically defective children; quantitation of the presence and importance of Th2 lymphocyte activation in human tuberculosis; the role of local conversion of inactive cortisone to active cortisol in the lesions; the recognition that some effective prophylactic vaccines also work as immumotherapeutics whereas others do not. In the longer term the recent sequencing of the M. tuberculosis genome will lead to further advances.In the short term, effective immunotherapy remains the most accessible breakthrough in the management of tuberculosis. The types of practical advance that will result from sequencing the genome are discussed speculatively, but cannot yet be predicted with certainty.

Mycobacteria, genes and the ‘hygiene hypothesis’

“…Interestingly, many of the observed effects of M. vaccae bear a resemblance to the inhibition of allergic asthma symptoms after glucocorticoid treatment. It has been suggested that (myco)bacterial infections directly, or indirectly, via neural pathways, activate the hypothalamus-pituitary gland-adrenal gland to secrete glucorticoids [45,46], which subsequently may reduce allergic inflammation.…”

Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83

“…These staggering numbers make TB one of the leading infectious disease killers. [1][2][3][4] The situation is worsened by the increasing incidence of both multidrug-resistant strains and combined infection with TB and AIDS. The chemotherapeutic regimens available for treatment of TB are far from ideal, requiring the ingestion of multiple anti-TB drugs over prolonged periods.…”

Immunomodulatory Role of Mycobacterial PE/PPE Family of Proteins

“…Successful elimination of M.tb bacteria depends mainly on the interactions between infected macrophages and antigen-specific T-cells (Kaufmann and Flesch, 1988). Immunity to M.tb depends on robust Th1 cell-mediated response while susceptibility is associated with Th2 response (Rook et al, 2001). Among the several factors that regulate naïve T cell polarization and development into Th1or Th2 cell, the cytokines produced by activated macrophages and dendritic cells (DC) have the most influential role (Netea et al, 2005).…”