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Volume 148, Issue 10

-infected human macrophages exhibit enhanced cellular adhesion with increased expression of LFA-1 and ICAM-1 and reduced expression and/or function of complement receptors, FcγRII and the mannose receptor Free

Abstract

The entry of () 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 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 -infected macrophages over time was examined, using inverted-phase microscopy and an culture model of human monocyte-derived macrophages (MDMs). Prior to and immediately following infection of the MDMs with , the macrophages appeared as individual cells in monolayer culture; however, within 24 h of infection with , 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 FcγRII, 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 -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

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): AM, alveolar macrophage , EC3bi, C3bi-coated erythrocytes , granuloma , HK, heat-killed , HRP, horseradish peroxidase , ICAM-1, counter receptor of LFA-1 , integrin , LFA-1, lymphocyte function-associated antigen-1 , major histocompatibility complex Class II (MHC-II) , MDM, monocyte-derived macrophage , MHC-II, major histocompatibility complex Class II , Mtb, Mycobacterium tuberculosis , phagocytosis , TEM, transmission electron microscopy and tubercle bacillus
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2002-10-01
2024-04-19
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Mycobacterium tuberculosis-infected human macrophages exhibit enhanced cellular adhesion with increased expression of LFA-1 and ICAM-1 and reduced expression and/or function of complement receptors, FcγRII and the mannose receptor
Microbiology 148, 3161 (2002); https://doi.org/10.1099/00221287-148-10-3161
/content/journal/micro/10.1099/00221287-148-10-3161
/content/journal/micro/10.1099/00221287-148-10-3161
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