InlB protein secreted by Listeria monocytogenes controls the pathogen interaction with macrophages

Abstract

The virulence of gram-positive bacterium Listeria monocytogenes depends on its capacity to infect non-professional phagocytes and proliferate inside them. Listerias monocytogenes captured by mononuclear phagocytic cells during the infectious process are resistant to lysosomal digestion and can proliferate inside macrophages. Internalin B (InlB), one of the key pathogenicity factors of L. monocytogenes, interacts with mammalian receptors c-Met and gC1q-R. For epithelial cells, such interactions with surface receptors promote activation of these receptors and cytoskeletal remodeling, which leads to massive bacterial invasion into nonprofessional phagocytes. For macrophages, by contrast, nothing is known about the role of InlB in their interactions with L. monocytogenes apart from the fact that both receptors are abundantly expressed by macrophages and participate in the development of immune reactions. This study aimed at determination of the potential role of InlB in the interactions between L. monocytogenes and macrophages. We found that 1) InlB expression promoted a significant 3.5-fold increase in the rates of L. monocytogenes capture by macrophages; 2) the 24 h fold increase in bacterial number inside macrophages constituted 182.5 ± 16.7, 96 ± 12 and 13.3 ± 3 for EGDe∆inlB, EGDe and EGDe∆inlB::pInlB strains, respectively; 3) the EGDe∆inlB::pInlB strain, complemented with a plasmid copy of inlB, produced InlB at 3.3fold higher rates than the type strain EGDe. We conclude that InlB negatively affects the survival of listeria inside macrophages. The results enable advanced understanding of the host-pathogen interactions for L. monocytogenes.