Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages.

During initial infection with Mycobacterium tuberculosis, bacteria that reach the distal airspaces of the lung are phagocytosed by alveolar macrophages in the presence of pulmonary surfactant. Here we have examined the role of surfactant-associated protein A (SP-A) in phagocytosis of the virulent Erdman strain of M. tuberculosis by human monocyte-derived macrophages (MDMs) and human alveolar macrophages (HAMs). Macrophage monolayers incubated with soluble SP-A from alveolar proteinosis patients (APP SP-A4) and recombinant rat SP-A (SP-Ahyp) demonstrated enhanced adherence of M. tuberculosis, 82 +/- 17% and 49 +/- 18%, respectively. Removal of SP-A from monolayers by washing before adding bacteria did not diminish the enhanced adherence. Fluorescence microscopy demonstrated that washed monolayers contained intracellular rather than surface-bound SP-A. These studies indicated a direct interaction between SP-A and the macrophage in mediating enhanced adherence of M. tuberculosis. Consistent with this interpretation, macrophage monolayers formed on human or rat SP-A (substrate SP-A) demonstrated enhanced adherence of M. tuberculosis to their apical surface (APP SP-A and native rat SP-A increased M. tuberculosis adherence by 102 +/- 16% and 102 +/- 25%, respectively). Electron microscopy demonstrated increased numbers of phagocytosed bacteria in APP SP-A-treated MDM cross-sections. SP-A proteins devoid of carbohydrate failed to enhance M. tuberculosis adherence to macrophages. In contrast, heat-denatured APP SP-A enhanced adherence of bacteria equivalent to that of intact glycoprotein. Thus, the carbohydrate moieties of SP-A appear to be critical in the SP-A-macrophage interaction. Finally, mannan and anti-mannose receptor Ab completely inhibited the enhanced phagocytosis of M. tuberculosis observed with APP SP-A, providing evidence for up-regulation of macrophage mannose receptor activity. These studies implicate SP-A as an important modulator of alveolar macrophage function that results in an enhanced potential for M. tuberculosis to gain access to its intracellular niche.

Disseminated Mycobacterium genavense infection in two patients with AIDS.

Mycobacterium genavense is a recently defined fastidious organism that has been identified as a cause of disseminated infection in patients with AIDS. We report the cases of two patients who had advanced AIDS and a clinical syndrome of fever, anorexia, abdominal pain, diarrhea, and weight loss. In addition, splenomegaly and lymphadenopathy were prominent in both cases, and in one patient's case radiographic findings were suggestive of splenic abscesses. Mycobacteria isolated from specimens of blood and bone marrow grew in liquid media but not on solid media. The results of DNA probe tests for Mycobacterium tuberculosis and Mycobacterium avium complex were false-positive for both patients. After treatment of the broth cultures to lyse red blood cells, the results of DNA probe tests were negative for these pathogens. Amplification and sequencing of 16S rRNA with use of the polymerase chain reaction indicated that the mycobacterial isolates from both patients had sequences identical to those previously reported for M. genavense. One patient survived 5 months after diagnosis, the other 2 months after diagnosis; only one patient responded (transiently) to antimycobacterial chemotherapy.