Taking Toll of TB

Abstract

TB is still a major killer worldwide; one-third of the population is infected with Mycobacterium tuberculosis, the agent that causes pulmonary TB. The TB problem has been worsened by the HIV epidemic and the emergence of drug-resistant strains of M. tuberculosis, and aggravated even further by the failure of currently available vaccines in field trials. There is therefore a pressing need to develop novel treatments that do not depend on new antibiotics.The mammalian immune response to microbial pathogens comprises an early innate response followed by a more sustained adaptive immunity. Macrophages and other phagocytic cells ingest infectious agents at the site of infection and initiate an immune response in two ways: they produce inflammatory cytokines and present pathogen-derived antigens to the cells of adaptive immunity. Microbial ligands such as lipopolysaccharides and lipoproteins activate members of the highly conserved Toll-like-receptor (TLR) protein family on macrophages. It is known that TLRs facilitate the production of cytokines and regulate adaptive immunity, but their role in direct antimicrobial activity in mammals has been unclear. A recent report shows that alveolar macrophages internalize and destroy M. tuberculosis at the site of infection 1xInduction of direct antimicrobial activity through mammalian Toll-like receptors. Thoma-Uszynsky, S. et al. Science. 2001; 291: 1544–1547Crossref | PubMed | Scopus (506)See all