Interactions of Listeria monocytogenes with the Autophagy System of Host Cells.
Adv Immunol. 2012;113:7-18
Authors: Lam GY, Czuczman MA, Higgins DE, Brumell JH
Abstract
Macrophages are immune cells that participate in the host defense against bacterial pathogens. These cells mediate bacterial clearance by internalizing bacteria into a phagosome, which ultimately fuses with lysosomes to kill bacteria. One bacterial strategy to evade killing in the phagosome is to escape from this compartment prior to lysosomal fusion. Listeria monocytogenes is a classic example of a “cytosol-adapted pathogen” in that it can rapidly escape from the phagosome in macrophages (and other cell types) and replicate rapidly in the cytosol. Phagosome escape also enables cell-to-cell spread by the bacteria through a bacterial driven actin-based motility mechanism. How the bacteria escape the phagosome and evade host cellular defenses, including autophagy, will be discussed in this review. We also discuss an underappreciated population of L. monocytogenes that can replicate in macrophage vacuoles and how these may be important for the establishment of chronic infections.
Virulence factors that modulate the cell biology of listeria infection and the host response.
Adv Immunol. 2012;113:19-32
Authors: Mostowy S, Cossart P
Abstract
The Gram-positive bacterial pathogen Listeria monocytogenes has become one of the best studied models in infection biology. This review will update our knowledge of Listeria virulence factors and highlight their role during the Listeria infection process.
Dendritic Cells in Listeria monocytogenes Infection.
Adv Immunol. 2012;113:33-49
Authors: Edelson BT
Abstract
Dendritic cells (DCs) represent a unique collection of innate immune cells present throughout the body as distinct subpopulations generally sharing the functions of pathogen recognition, cytokine production, and antigen presentation. A large body of work in recent years has examined DC functions during infection with Listeria monocytogenes (Lm), particularly in the murine model. Here, I review several aspects of DC biology in this model, with particular emphasis on the role DCs play in the establishment of a productive Lm infection and the role of DCs as cytokine producers and antigen-presenting cells in this system.
Probing CD8 T Cell Responses with Listeria monocytogenes Infection.
Adv Immunol. 2012;113:51-80
Authors: Condotta SA, Richer MJ, Badovinac VP, Harty JT
Abstract
CD8 T cells play a critical role in the control and eradication of intracellular pathogens. Increased understanding of CD8 T cell biology provides insight that can be translated into improved vaccination strategies. The intracellular bacterium, Listeria monocytogenes, has been used as a model organism to study every phase of the CD8 T cell response to intracellular bacterial infection. Infection of laboratory mice with L. monocytogenes has provided insight into the factors that are involved in primary T cell responses, memory CD8 T cell generation, maintenance, functionality, and diversification following repeated pathogenic challenges. In this review, we will focus on work from our laboratories utilizing the murine model of L. monocytogenes to investigate the characteristics of CD8 T cell responses to infection. This model has profoundly advanced our understanding of the CD8 T cell response to infection and is likely to continue to provide invaluable basic insights that can be translated into the development of effective vaccination strategies to protect against pathogens.
Listeria monocytogenes and Its Products as Agents for Cancer Immunotherapy.
Adv Immunol. 2012;113:81-118
Authors: Guirnalda P, Wood L, Paterson Y
Abstract
This review covers the use of Listeria monocytogenes and its virulence factors as cancer immunotherapeutics. We describe their development as vectors to carry protein tumor antigen and eukaryotic DNA plasmids to antigen-presenting cells and efforts to harness their tumor-homing properties. We also describe their use as vectors of angiogenic molecules to induce an immune response that will destroy tumor vasculature. The background knowledge necessary to understand the biology behind the rationale to develop Listeria as a vaccine vector for tumor immunotherapy is included as well as a brief summary of the major therapies that have used this approach thus far.
Monocyte-Mediated Immune Defense Against Murine Listeria monocytogenes Infection.
Adv Immunol. 2012;113:119-34
Authors: Serbina NV, Shi C, Pamer EG
Abstract
Infection of mice with Listeria monocytogenes induces a robust innate inflammatory response that restricts bacterial growth in the liver and spleen prior to the development of protective T cell responses. Ly6C(hi) monocytes contribute to the innate immune response following L. monocytogenes infection and in their absence, mice rapidly succumb to infection. Emigration of Ly6C(hi) monocytes from the bone marrow into the circulation is the first step in their recruitment to sites of L. monocytogenes infection and is triggered by CCL2- and CCL7-mediated stimulation of CCR2 chemokine receptors on monocytes. CCL2 expression by mesenchymal stem cells in the bone marrow, in response to TLR stimulation, drives monocyte emigration from cellular compartments into vascular sinuses of the bone marrow. In addition to TLR ligands, type I interferon-mediated signals can also drive monocyte emigration from the bone marrow during L. monocytogenes infection. Once Ly6C(hi) monocytes enter the bloodstream, trafficking to sites of infection in the liver and spleen is CCR2 independent. In the liver, CD11b on the monocyte and ICAM-1 on the surface of endothelial cells target Ly6C(hi) monocytes to foci of L. monocytogenes infection. At the site of infection, Ly6C(hi) monocytes undergo MyD88-dependent differentiation into TNF and iNOS-producing dendritic cells (TipDCs) and express MHC class II, B7.1, and CD40 on their cell surface. How TipDCs mediate bacterial clearance during early L. monocytogenes infection remains an active area of investigation.
Innate Immune Pathways Triggered by Listeria monocytogenes and Their Role in the Induction of Cell-Mediated Immunity.
Adv Immunol. 2012;113:135-56
Authors: Witte CE, Archer KA, Rae CS, Sauer JD, Woodward JJ, Portnoy DA
Abstract
Acquired cell-mediated immunity to Listeria monocytogenes is induced by infection with live, replicating bacteria that grow in the host cell cytosol, whereas killed bacteria, or those trapped in a phagosome, fail to induce protective immunity. In this chapter, we focus on how L. monocytogenes is sensed by the innate immune system, with the presumption that innate immunity affects the development of acquired immunity. Infection by L. monocytogenes induces three innate immune pathways: an MyD88-dependent pathway emanating from a phagosome leading to expression of inflammatory cytokines; a STING/IRF3-dependent pathway emanating from the cytosol leading to the expression of IFN-β and coregulated genes; and very low levels of a Caspase-1-dependent, AIM2-dependent inflammasome pathway resulting in proteolytic activation and secretion of IL-1β and IL-18 and pyroptotic cell death. Using a combination of genetics and biochemistry, we identified the listerial ligand that activates the STING/IRF3 pathway as secreted cyclic diadenosine monophosphate, a newly discovered conserved bacterial signaling molecule. We also identified L. monocytogenes mutants that caused robust inflammasome activation due to bacteriolysis in the cytosol, release of DNA, and activation of the AIM2 inflammasome. A strain was constructed that ectopically expressed and secreted a fusion protein containing Legionella pneumophila flagellin that robustly activated the Nlrc4-dependent inflammasome and was highly attenuated in mice, also in an Nlrc4-dependent manner. Surprisingly, this strain was a poor inducer of adaptive immunity, suggesting that inflammasome activation is not necessary to induce cell-mediated immunity and may even be detrimental under some conditions. To the best of our knowledge, no single innate immune pathway is necessary to mount a robust acquired immune response to L. monocytogenes infection.
Mechanisms and immunological effects of apoptosis caused by listeria monocytogenes.
Adv Immunol. 2012;113:157-74
Authors: Carrero JA, Unanue ER
Abstract
Infection with Listeria monocytogenes shows an early stage of lymphocyte apoptosis. This is an obligatory stage the extent of which depends on infective dose. Lymphocyte apoptosis occurs early and is rapidly superseded, yet it has a strong biological consequence. The immunological effect of lymphocyte apoptosis following infection is increased susceptibility to L. monocytogenes infection due, in part, to upregulation of IL-10 on macrophages and DC. Lymphocyte apoptosis is dependent on bacterial expression of the pore-forming toxin listeriolysin O (LLO). Also, purified LLO can lead to the induction of death pathways similar to infection, demonstrating that it is a killer agent generated by L. monocytogenes. Signaling through the type I interferon receptor potentiates cell death induced by the bacteria or LLO. Infection with L. monocytogenes also causes death of phagocytic cells, the nature and significance of which is not clear at present. Infection with L. monocytogenes is a tractable model to examine pathogen-induced cell death pathways and their possible immunological consequences in multiple cell types following infection.
Regulatory T (Treg) cells expressing the transcription factor Foxp3 constitute a unique T-cell lineage committed to suppressive functions and play a central role in maintaining self-tolerance and immune homeostasis. While their differentiation state is remarkably stable in the face of various perturbations from the extracellular environment, recent studies have also revealed their adaptability to the changing environment; in response to extrinsic cues, Treg cells differentiate further into distinct substates to regulate different classes of immune responses effectively. In contrast, some other recent studies have challenged this notion of a committed Treg cell lineage and suggested that Treg cells might lose their identity and be reprogrammed to various effector helper T cells under certain circumstances, although this issue of environment-induced Treg cell reprogramming remains highly controversial. This review will focus on recent advances in our understanding of how the stability and adaptability of Treg cell lineage is regulated and how it might be perturbed in a changing environment.
PMID: 22118405 [PubMed - in process]
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