Lymphocytes serve as a reservoir for Listeria monocytogenes growth during infection of mice

Abstract

It is widely reported that Listeria monocytogenes can infect virtually all cell types, however, the degree to which this facultative intracellular pathogen can infect lymphocytes has not been well characterized. Previous studies have shown that a subset of lymphocytes, including activated T cells, are susceptible to apoptosis following exposure to L. monocytogenes, but the ability of the bacteria to replicate in the cytosol of lymphocytes prior to cell death was not examined. In this report, we demonstrate that intracellular L. monocytogenes can survive and multiply in vitro in a variety of transformed cell lines of lymphocytic origin. Intracellular L. monocytogenes were also recovered from splenic B cells, T cells, and NK cells following intravenous infection of mice. In fact, lymphocyte-associated L. monocytogenes comprised a substantial portion of the total bacterial burden in the spleen throughout the course of murine infection and B cell deficient mice had significantly lower titers of bacteria present in the spleen following intravenous infection. These results suggest that lymphocytes can be a reservoir for L. monocytogenes growth in vivo.

Monocytes Are the Predominant Cell Type Associated with Listeria monocytogenes in the Gut, but They Do Not Serve as an Intracellular Growth Niche

“…The primary virulence strategy of L. monocytogenes is thought to be the ability to invade mammalian cells. L. monocytogenes survive and replicate inside a wide variety of cell types including epithelial cells (1), endothelial cells (2), hepatocytes (3), lymphocytes (4), cardiomyocytes (5), and neurons (6). L. monocytogenes induce uptake into non-phagocytic epithelial and endothelial cells using internalin A (InlA) and internalin B to interact with the mammalian receptors, E-cadherin and c-Met, respectively (7).…”

T Cells Capture Bacteria by Transinfection from Dendritic Cells

“…T cells are refractory to being infected in vitro but some reports indicate that they can be infected in vivo 14,15 . The intimate contacts of APC and T cells during immune synapse serve as platforms for exchanging biological material 13 , including some viruses such as HIV 11 .…”

“…The intimate contact between APCs and lymphocytes that take place during the course of IS formation also function as a platform for exchange of part of membranes, genetic material and exosomes and can be hijacked for some viruses to infect T cells; this process is called transinfection [11][12][13] . Some pathogenic bacteria (Listeria monocytogenes, Salmonella enterica and Shigella flexneri) are able to invade T lymphocytes in vivo and modify their behaviour [14][15][16] . We have recently described that T lymphocytes are also able to capture bacteria by transinfection from previously infected dendritic cells (DCs) during the course of antigen presentation 16 .…”

The Role of Natural Killer Cells in the Defense against <i>Listeria</i><i>monocytogenes</i> Lessons from a Rat Model

“…However, bacteria that escape these initial defense mechanisms may give rise to serious systemic infections. Listeria primarily infects macrophages (M), dendritic cells (DCs), hepatocytes and intestinal epithelial cells, but fibroblasts, endothelial cells, neurons and even lymphocytes including natural killer (NK) cells may be susceptible [7,8] . Listeria is taken up by M by binding to polysaccharide receptors or type I M scavenger receptors [4,6] .…”

“…After internalization, Listeria must be able to escape from the vacuole/phagosome before fusion with lysosomes in order to survive. This key process is dependent on listeriolysin O, an enzyme that lyses the endosomal membrane and is a central virulence factor for Listeria [8] . The escape from phagosomes is enhanced by bacterial phospholipase C [9] .…”