Immunopathology of tuberculosis : roles of macrophages and monocytes

Robert Koch identified Mycobacterium tuberculosis as the causative agent of tuberculosis (TB) in 1882 and was the first to realize that the efficacy of his early tuberculin therapies depended largely on the strength of the patient's immune response. Recent understanding of the roles played by leukocytes and the cytokines they secrete has revealed much about the delicate underlying balance between the strategies used by M. tuberculosis to survive within a host and the concomitant efforts of the host to kill it. In this article, we review the current state of understanding of the roles played by mononuclear phagocytes in response to inhaled M. tuberculosis. Archeological evidence indicates that TB has afflicted humans for thousands of years. Following a 30-year period in which the incidence of TB in the United States declined by about 5% per year, this figure has begun to rise again. Between 1985 and 1992, TB cases in the United States increased by about 20%. This resurgence has been linked to the spread of human immunodeficiency virus (HIV) and to a combination of demographic and socioeconomic factors that have acted in concert to maintain a reservoir of infected persons. A recent report by the World Health Organization predicts that by the year 2005, TB will kill 4 million people annually. This is a significant increase from an estimated 3 million deaths worldwide caused by TB in 1992. While TB is a preventable and largely curable disease, our understanding of the cellular and molecular interactions between mycobacteria and host immune cells is far from complete, and the topic presents significant research challenges.