Innate and Adaptive Immune Responses duringListeria monocytogenesInfection

Abstract

It could be argued that we understand the immune response to infection with Listeria monocytogenes better than the immunity elicited by any other bacteria. L. monocytogenes are Gram-positive bacteria that are genetically tractable and easy to cultivate in vitro , and the mouse model of intravenous (i.v.) inoculation is highly reproducible. For these reasons, immunologists frequently use the mouse model of systemic listeriosis to dissect the mechanisms used by mammalian hosts to recognize and respond to infection. This article provides an overview of what we have learned over the past few decades and is divided into three sections: “Innate Immunity” describes how the host initially detects the presence of L. monocytogenes and characterizes the soluble and cellular responses that occur during the first few days postinfection; “Adaptive Immunity” discusses the exquisitely specific T cell response that mediates complete clearance of infection and immunological memory; “Use of Attenuated Listeria as a Vaccine Vector” highlights the ways that investigators have exploited our extensive knowledge of anti- Listeria immunity to develop cancer therapeutics.

Neutrophils Are More Effective than Monocytes at Phagosomal Containment and Killing ofListeria monocytogenes

“…This study lends credence to previous conclusions of neutrophils being the primary innate cells that associate with and phagocytose L. monocytogenes early on during infection (7,10,32). Although neutrophils and monocytes are rapidly mobilized to L. monocytogenes foci during infection, the neutrophils are more important for bacterial uptake as they observably took up more bacteria overall in comparison with monocytes.…”

“…The innate immune response has been shown to be necessary for host protection during L. monocytogenes infection (7). Specifically, neutrophils, macrophages, and monocytes are essential for protection, as mice that lack any of these cells experience increased susceptibility to L. monocytogenes infection (2).…”

Why isListeria monocytogenessuch a potent inducer of CD8+ T‐cells?

“…Although natural infection is clearly via the oral route, most basic research has been conducted in mice using either intravenous or intraperitoneal routes of administration. Indeed, beginning with the classic work of George Mackaness in the 1960s, L. monocytogenes emerged as a highly quantitative and reproducible murine model system to study basic aspects of innate and adaptive immunity (D'Orazio, ; Mackaness, ; McGregor, Koster, & Mackaness, ). To very briefly summarise decades of research, an effective innate immune response to L. monocytogenes is sufficient to contain the infection and relies on the orchestrated influx of neutrophils and macrophages to the sites of infection followed by the activation of macrophage bactericidal activity.…”

“…The hallmark of adaptive immunity to L. monocytogenes is that naïve mice that recover from a primary challenge develop long-term immunity to reinfection (Condotta, Richer, Badovinac, & Harty, 2012;D'Orazio, 2019). The most common assay used to measure adaptive immunity is to infect immunised mice with a dose of L. monocytogenes lethal to nonimmunised mice and determine the number of colonyforming units in the liver and spleen after 48 or 72 hr compared with the numbers observed in nonimmunised mice.…”

“…as a highly quantitative and reproducible murine model system to study basic aspects of innate and adaptive immunity (D'Orazio, 2019;Mackaness, 1962;McGregor, Koster, & Mackaness, 1970). To very briefly summarise decades of research, an effective innate immune response to L. monocytogenes is sufficient to contain the infection and relies on the orchestrated influx of neutrophils and macrophages to the sites of infection followed by the activation of macrophage bactericidal activity.…”