Host defense against nontuberculous mycobacterial infections.
Human contact with the nontuberculous mycobacteria (NTM) is quite common, yet serious infections with these organisms were relatively infrequent until the advent of AIDS. Mycobacteria present an important window on the interaction of the innate (neutrophils, macrophages, NK cells) and acquired (T cells and B cells) immune systems. In their attempt to infect macrophages, the mycobacteria use their complex glycopeptidolipid cell wall to down-regulate macrophage responses. Once inside, mycobacteria are subject to the panoply of primary macrophage responses (e.g., vacuolar acidification, lytic enzymes). The infected macrophage produces cytokine signals (e.g., chemokines, interleukin [IL]-12] that recruit and stimulate lymphocytes from the innate (NK cell) and acquired (T and B cells) arms of the immune response to help kill the invading mycobacteria. Lymphocyte products that are central to the activation of macrophages to increased mycobacterial killing include tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The precise mechanisms by which these cytokines work remains unknown. Rare patients who have refractory disseminated NTM infection without HIV infection probably have underlying immune defects in critical pathways for control of mycobacteria. We have recently characterized one such family and found abnormal IL-12 regulation. Interferon-gamma, the cytokine primarily elicited by IL-12, has been used successfully with antimycobacterials for treatment of these patients. The window on the interaction of the innate and acquired immune systems that mycobacteria afford is being opened. Understanding the cell-cell interactions and cytokines involved in NTM infections will lead to new therapeutic approaches.
Holland
S M
SM
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886, USA.
D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007121:Immunocompetence / Q000502:physiology; D009164:Mycobacterium Infections / Q000276:immunology*