The entry of Mycobacterium tuberculosis (Mtb) into the host macrophage and its survival in this environment are key components of
tuberculosis pathogenesis. Following intracellular replication of the bacterium within alveolar macrophages, there is spread of bacilli to regional lymph nodes in the lungs and subsequent presentation of
antigens to the host immune system. How this process occurs remains poorly understood, but one mechanism may involve the migration of macrophages containing Mtb across the alveoli to lymph nodes, where there is development of a protective host response with formation of
granulomas composed in part of aggregated and fused, apoptotic, infected macrophages. Leukocyte
integrins, including
lymphocyte function-associated antigen-1 (LFA-1) and
complement receptors CR3 and CR4, and their counter receptors play a major role in macrophage adhesion processes and phagocytosis. In this study, the appearance of Mtb-infected macrophages over time was examined, using inverted-phase microscopy and an in vitro culture model of human monocyte-derived macrophages (MDMs). Prior to and immediately following
infection of the MDMs with Mtb, the macrophages appeared as individual cells in monolayer culture; however, within 24 h of
infection with Mtb, the MDMs began to migrate and adhere to each other. The kinetics of this response were dependent on both the m.o.i. and the length of
infection. Quantitative transmission electron microscopy studies revealed that macrophage adhesion was accompanied by increases in levels of
LFA-1 and its counter receptor (ICAM-1), decreases in surface levels of the phagocytic receptors CR3, CR4 and FcgammaRII, and an increase in major histocompatibility complex Class II (
MHC-II) molecules at 72 h post-
infection. Decreases in surface levels of CR3 and CR4 had a functional correlate, with macrophages containing live bacilli showing a diminished phagocytic capacity for
complement-opsonized sheep erythrocytes; macrophages containing heat-killed bacilli did not show this diminished capacity. The modulation of macrophage adhesion and phagocytic
proteins may influence the trafficking of Mtb-infected macrophages within the host, with increases in levels of
LFA-1 and
ICAM-1 enhancing the adhesive properties of the macrophage and decreases in phagocytic receptors diminishing the phagocytic capacity of an already-infected cell, potentially allowing for maintenance of the intracellular niche of Mtb.