Entry of Mycobacterium tuberculosis into Mononuclear Phagocytes

Abstract

Mycobacterium tuberculosis is one of a diverse group of intracellular pathogens that survives the process of entry into mammalian cells. Multiplication within the cell is critical for the pathogenesis of disease by these host-adapted microbes. For M. tuberculosis, the major host cell reservoir is the mononuclear phagocyte, including both monocytes and macrophages. These cells, along with polymorphonuclear leukocytes, are considered professional phagocytes in that they have adapted specifically to engulf and destroy bacteria or other foreign particulate matter. Given the potent microbiocidal mechanisms that these cells possess, M. tuberculosis has adapted strategies to circumvent adverse host cellular responses during and after entry. The earliest interaction between M. tuberculosis and the mononuclear phagocyte is binding of the bacterium to the cell surface and subsequent internalization. Specific receptor-ligand interactions mediate this internalization and the outcome of one interaction may be different than the outcome of another (Fig. 1). For example, it can be only attachment of the bacterium, which for M. tuberculosis may be less important for disease pathogenesis, or it can be ingestion (phagocytosis), which in turn can lead to either intracellular survival or death of the bacterium. Recent studies provide evidence for the importance of specific receptor-ligand pathways (single or multiple) and cooperativity between receptors in dictating the fate of phagocytosed intracellular pathogens (Joiner et al. 1990; Mosser and Edelson 1987; Drevets et al. 1992; Hoepelman and Tuomanen 1992; Hieny et al. 1992).