Invasion of the Brain by Listeria monocytogenes Is Mediated by InlF and Host Cell Vimentin

Abstract

Listeria monocytogenes is a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability of L. monocytogenes to breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood. Here we show that L. monocytogenes is able to utilize vimentin for invasion of host cells. Vimentin is a type III intermediate filament protein within the cytosol but is also expressed on the host cell surface. We found that L. monocytogenes interaction with surface-localized vimentin promoted bacterial uptake. Furthermore, in the absence of vimentin, L. monocytogenes colonization of the brain was severely compromised in mice. The L. monocytogenes virulence factor InlF was found to bind vimentin and was necessary for optimal bacterial colonization of the brain. These studies reveal a novel receptor-ligand interaction that enhances infection of the brain by L. monocytogenes and highlights the importance of surface vimentin in host-pathogen interactions.

Release of astroglial vimentin by extracellular vesicles: Modulation of binding and internalization of C3 transferase in astrocytes and neurons

“…Secreted vimentin could also be detected in vitro in astrocyte-conditioned medium (Greco, Seeholzer, Mak, Spruce, & Ischiropoulos, 2010) and has been described for other cell types like macrophages and neutrophils (Moisan & Girard, 2006;Mor-Vaknin, Punturieri, Sitwala, & Markovitz, 2003). Functionally, extracellular vimentin is involved in binding to bacterial or viral pathogens (Ghosh et al, 2018;Yu et al, 2016). In the context of astrocyte-neuron interactions, it was shown that C-terminal residues of secreted vimentin can bind to the neuronal insulin-like growth factor 1 receptor, thereby stimulating its phosphorylation and axonal outgrowth of cultured neocortical neurons (Shigyo, Kuboyama, Sawai, Tada-Umezaki, & Tohda, 2015).…”

Listeria monocytogenes isolates from ready to eat plant produce are diverse and have virulence potential

“…Whole genome sequences of isolates revealed that all strains contained the hly (listeriolsyin O) gene and all strains had the internalin family of genes present (inlA, inlB, inlC, inlF, inlJ, inlK) except strain NLmo18, where inlF was missing. This gene codes for a protein that mediates invasion of the brain of the host by binding with vimentin (Ghosh et al, 2018) and suggest that…”

Neurotropic Lineage III Strains of Listeria monocytogenes Disseminate to the Brain without Reaching High Titer in the Blood

“…Three mechanisms have been proposed to explain how L. monocytogenes disseminates to the brain: direct invasion of the blood-brain barrier, transport inside or attached to a migratory immune cell, and axonal migration. Recent work showed that the L. monocytogenes surface protein InlF is important for optimal invasion of brain endothelial cells in vitro and colonization of the murine brain following intravenous inoculation ( 14 ). Systemic listeriosis induces proinflammatory cytokine expression in the brain that precedes an influx of Ly6C hi monocytes, and L. monocytogenes has been found associated with those infiltrating cells ( 15 – 18 ).…”

“…Hematogenous spread of L. monocytogenes can be modeled in mice by intravenously injecting large doses of reference strains such EGD or 10403s ( 14 , 15 ). Early studies indicated that a prolonged bacteremia with 10 2 to 10 3 CFU/ml of blood was needed for brain colonization ( 21 , 22 ).…”