Pulmonary
collectins,
surfactant proteins A (SP-A) and D (
SP-D), play important roles in innate immunity of the lung. Legionella pneumophila is a bacterial respiratory pathogen that can replicate within macrophages and causes
opportunistic infections. L. pneumophila possesses cytolytic activity, resulting from insertion of pores in the macrophage membrane upon contact. We examined whether pulmonary
collectins play protective roles against L. pneumophila
infection. SP-A and
SP-D bound to L. pneumophila and its
lipopolysaccharide (LPS) and inhibited the bacterial growth in a Ca(2+)-dependent manner. The addition of LPS in the culture blocked the inhibitory effects on L. pneumophila growth by the
collectins, indicating the importance of LPS-
collectin interaction. When differentiated THP-1 cells were infected with L. pneumophila in the presence of SP-A and
SP-D, the number of permeable cells was significantly decreased, indicating that pulmonary
collectins inhibit pore-forming activity of L. pneumophila. The number of live bacteria within the macrophages on days 1-4 after
infection was significantly decreased when
infection was performed in the presence of pulmonary
collectins. The phagocytosis experiments with the pH-sensitive
dye-labeled bacteria revealed that pulmonary
collectins promoted bacterial localization to an acidic compartment. In addition, SP-A and
SP-D significantly increased the number of L. pneumophila co-localized with LAMP-1. These results indicate that pulmonary
collectins protect macrophages against contact-dependent cytolytic activity of L. pneumophila and suppress intracellular growth of the phagocytosed bacteria. The promotion of lysosomal fusion with Legionella-containing phagosomes constitutes a likely mechanism of L. pneumophila growth suppression by the
collectins.