Nonopsonic and Opsonic Association of Mycobacterium tuberculosis with Resident Alveolar Macrophages Is Inefficient

Abstract

The association of Mycobacterium tuberculosis with alveolar macrophages (Mφ) in a serum-free environment is a crucial first step in the pathogenesis of this facultative intracellular pathogen. We present data demonstrating that freshly explanted alveolar Mφ do not efficiently bind M. tuberculosis in a serum-free system, although a small subpopulation of these Mφ (10–15%) can bind mycobacteria. In contrast, almost 100% of a peritoneal Mφ population bind mycobacteria under the same conditions. The poor binding of mycobacteria by alveolar Mφ does not reflect a general inability to associate with particles; binding and ingestion of latex beads and zymosan particles were comparable with that seen with peritoneal Mφ. Resident alveolar Mφ did not efficiently bind mycobacteria in the presence of serum and expressed poorly several Mφ surface receptors, including CR3. Furthermore, we demonstrate that bovine surfactant protein A does not enhance the association of M. tuberculosis with alveolar Mφ. Differentiation of alveolar Mφ in vitro resulted in increased expression of Mφ surface receptors and an increased capacity to bind mycobacteria in the presence and absence of serum. Evidence is presented that opsonic binding of M. tuberculosis by differentiated alveolar Mφ is mediated by complement and CR3, and that the poor binding by resident alveolar Mφ is due to their poor expression of CR3. The receptor mediating nonopsonic binding of M. tuberculosis to differentiated alveolar Mφ was not unequivocally identified in this study, but could also be CR3.