Adherence and uptake of Francisella into host cells

Abstract

Francisella tularensis is a highly virulent bacterial pathogen that is easily aerosolized and has a low infectious dose. As an intracellular pathogen, entry of Francisella into host cells is critical for its survival and virulence. However, the initial steps of attachment and internalization of Francisella into host cells are not well characterized, and little is known about bacterial factors that promote these processes. This review highlights our current understanding of Francisella attachment and internalization into host cells. In particular, we emphasize the host cell types Francisella has been shown to interact with, as well as specific receptors and signaling processes involved in the internalization process. This review will shed light on gaps in our current understanding and future areas of investigation.

Keywords: Francisella tularensis; LVS; adherence; attachment; internalization; novicida.

Figure 1. Overview of initial interactions between Francisella tularensis and host cells. Francisella attaches to the host cell surface via the bacterial pilus, FsaP, bacterial elongation factor-Tu (EF-Tu), uncharacterized adhesins (??), or opsonins. Host cell ligands for the pilus and FsaP have not been characterized (??). Once adhered, bacteria engage in specific adhesin–host receptor interactions to mediate internalization. In the absence of opsonins, Francisella engages the mannose receptor (MR), macrophage scavenger receptor (SRA), and surface nucleolin or uncharacterized receptors (??) to initiate uptake. In the presence of opsonins, Francisella internalization is redirected to the FcγR for antibody opsonized (Abs), or complement receptors (CR) and scavenger receptor (SRA) for serum-opsonized with C3b or C3bi. Opsonins bound by SRA have not been elucidated. Lung surfactant protein A (SP-A) can also serve as an opsonin to enhance internalization of Francisella.