A Comparison of Oral and Intravenous Mouse Models of Listeriosis

Abstract

Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal model of listeriosis over the past few decades. The infection is highly reproducible and has been invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly CD8+ T cell responses to intracellular pathogens. However, the i.v. model completely bypasses the gut phase of the infection. Recent advances in generating both humanized mice and murinized bacteria, as well as the development of a foodborne route of transmission has reignited interest in studying oral models of listeriosis. In this review, we analyze previously published reports to highlight both the similarities and differences in tissue colonization and host response to infection using either oral or i.v. inoculation.

CD8+ T cell priming in oral mucosa-draining lymph nodes supports systemic immunity

“…1F ). This is in line with the notion that > 90% of ingested bacteria are killed by gastric acids (Saklani-Jusforgues et al, 2000; Pitts and D’Orazio, 2018). Residual Lm in the intestinal lumen may have been degraded by digestive enzymes, or failed to cross the mucus layer of the intestinal epithelium or their tight junctions, or become cleared by peristaltic contraction and mucus secretion.…”

Contributions of a LysR Transcriptional Regulator to Listeria monocytogenes Virulence and Identification of Its Regulons

“…The i.p. route allows Listeria to disseminate systemically via the lymphatic system and blood, but it bypasses the need for invasion of the intestine, as occurs in oral infection (22). Previous work showed that the disruption of LTTR family members caused a loss of virulence.…”

The Novel Internalins InlP1 and InlP4 and the Internalin-Like Protein InlP3 Enhance the Pathogenicity of Listeria monocytogenes

“…To investigate the role of InlP1, InlP3, InlPq, and InlP4 in the pathogenesis in vivo , we used an oral mouse infection model that allows a close imitation of the natural transmission route and the host environment including gastric stress despite the higher deviation in CFU counts that accompanies oral infection. The CFU deviation is due to individual responses in the mice in comparison to intravenous infection based on the fact that orally acquired bacteria have to pass a series of bottlenecks to reach target organs for colonization (Pitts and D’Orazio, 2018). We explicitly did not use an intravenous mouse infection model because listeriosis is not initiated by high bacterial loads in the blood and the colonization of peripheral tissues can be affected by preliminary colonization of the gut which is entirely avoided when L. monocytogenes is applied intravenously (Pitts and D’Orazio, 2018).…”

“…The CFU deviation is due to individual responses in the mice in comparison to intravenous infection based on the fact that orally acquired bacteria have to pass a series of bottlenecks to reach target organs for colonization (Pitts and D’Orazio, 2018). We explicitly did not use an intravenous mouse infection model because listeriosis is not initiated by high bacterial loads in the blood and the colonization of peripheral tissues can be affected by preliminary colonization of the gut which is entirely avoided when L. monocytogenes is applied intravenously (Pitts and D’Orazio, 2018). In general, oral L. monocytogenes mouse infection models distort the species-specific invasion process of the primary entry site that relies on the interaction between InlA, the most important virulence factor during invasion, and E-cadherin, the corresponding receptor on epithelial cells.…”

“…Since colonization of the small intestine, the liver and the spleen by orally acquired bacteria might take up to 48 h and can easily appear in asynchronous phases (Pitts and D’Orazio, 2018), we first determined the colonization efficiency at three time points in our experimental setting. Bacteria were detected in the small intestine 24, 48, and 72 h post infection with a significant decrease between 24 and 72 h. In contrast, sufficient colonization of the liver and spleen, the major target organs of L. monocytogenes replication, was detected only after 48 and 72 h in all animals, with a significant increase between 24 and 72 h. These time-dependent observations are in line with the innate infection route: L. monocytogenes encounters the small intestine as the primary entry site in the host where colonization occurs initially and decreases as the pathogen is shed via feces.…”