Immune responses to Listeria monocytogenes
TL;DR: A torrent of studies characterizing the contributions of different cytokines, receptors, adaptors and effector molecules to resistance against infection with Listeria monocytogenes yield one of the most comprehensive pictures of the 'battle' between host and microorganism.
Abstract: Listeria monocytogenes is a Gram-positive bacterium that is often used to study the mammalian immune response to infection because it is easy to culture, is relatively safe to work with and causes a highly predictable infection in laboratory mice. The broad application of this mouse model has resulted in a torrent of studies characterizing the contributions of different cytokines, receptors, adaptors and effector molecules to resistance against infection with Listeria monocytogenes. These studies, which are yielding one of the most comprehensive pictures of the 'battle' between host and microorganism, are reviewed here.
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TL;DR: The mechanisms that control monocyte trafficking under homeostatic, infectious and inflammatory conditions are being unravelled and are the focus of this Review.
Abstract: Monocytes originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues. During both homeostasis and inflammation, circulating monocytes leave the bloodstream and migrate into tissues where, following conditioning by local growth factors, pro-inflammatory cytokines and microbial products, they differentiate into macrophage or dendritic cell populations. Recruitment of monocytes is essential for effective control and clearance of viral, bacterial, fungal and protozoal infections, but recruited monocytes also contribute to the pathogenesis of inflammatory and degenerative diseases. The mechanisms that control monocyte trafficking under homeostatic, infectious and inflammatory conditions are being unravelled and are the focus of this Review.
2,309 citations
TL;DR: This review highlights the findings that have advanced the understanding of TGF-beta in the immune system and in disease.
Abstract: Transforming growth factor-beta (TGF-beta) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-beta in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-beta controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. The regulatory activity of TGF-beta is modulated by the cell differentiation state and by the presence of inflammatory cytokines and costimulatory molecules. Collectively, TGF-beta inhibits the development of immunopathology to self or nonharmful antigens without compromising immune responses to pathogens. This review highlights the findings that have advanced our understanding of TGF-beta in the immune system and in disease.
2,084 citations
TL;DR: In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations.
Abstract: Circulating blood monocytes supply peripheral tissues with macrophage and dendritic cell (DC) precursors and, in the setting of infection, also contribute directly to immune defense against microbial pathogens. In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations. Inflammatory monocytes respond rapidly to microbial stimuli by secreting cytokines and antimicrobial factors, express the CCR2 chemokine receptor, and traffic to sites of microbial infection in response to monocyte chemoattractant protein (MCP)-1 (CCL2) secretion. In murine models, CCR2-mediated monocyte recruitment is essential for defense against Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans infection, implicating inflammatory monocytes in defense against bacterial, protozoal, and fungal pathogens. Recent studies indicate that inflammatory monocyte recruitment to sites of infection is complex, involving CCR2-mediated emigration of monocytes from the bone marrow into the bloodstream, followed by trafficking into infected tissues. The in vivo mechanisms that promote chemokine secretion, monocyte differentiation and trafficking, and finally monocyte-mediated microbial killing remain active and important areas of investigation.
1,075 citations
TL;DR: Flavonoids are a family of plant-derived compounds with potentially exploitable activities, including direct antibacterial activity, synergism with antibiotics, and suppression of bacterial virulence, and recent advances towards understanding these properties are described.
985 citations
TL;DR: It is shown that mitochondrial metabolism in the absence of glucose metabolism is sufficient to support interleukin-2 (IL-2) induction and mitochondria are required for T cell activation to produce mROS for activation of nuclear factor of activated T cells (NFAT) and subsequent IL-2 induction.
928 citations
Cites background from "Immune responses to Listeria monocy..."
...Clearance of L. monocytogenes after infection is mediated by T cells, and CD8+ T cells provide the most substantial contribution to protective immunity (Pamer, 2004)....
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...monocytogenes after infection is mediated by T cells, and CD8 T cells provide the most substantial contribution to protective immunity (Pamer, 2004)....
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References
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TL;DR: It is reported that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-κB and stimulates tumour necrosis factor-α production, and the data suggest thatTLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flageLLated bacterial pathogens.
Abstract: The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, but not on the host. Toll-like receptors (TLRs) recognize PAMPs and mediate the production of cytokines necessary for the development of effective immunity. Flagellin, a principal component of bacterial flagella, is a virulence factor that is recognized by the innate immune system in organisms as diverse as flies, plants and mammals. Here we report that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha production. TLR5-stimulating activity was purified from Listeria monocytogenes culture supernatants and identified as flagellin by tandem mass spectrometry. Expression of L. monocytogenes flagellin in non-flagellated Escherichia coli conferred on the bacterium the ability to activate TLR5, whereas deletion of the flagellin genes from Salmonella typhimurium abrogated TLR5-stimulating activity. All known TLRs signal through the adaptor protein MyD88. Mice challenged with bacterial flagellin rapidly produced systemic interleukin-6, whereas MyD88-null mice did not respond to flagellin. Our data suggest that TLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flagellated bacterial pathogens.
3,575 citations
TL;DR: Toll-like receptors have been established to play an essential role in the activation of innate immunity by recognizing specific patterns of microbial components and TIR domain-containing adaptors provide specificity of TLR signaling.
2,291 citations
TL;DR: A novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo is reported and it is shown that in vivo DC are required to cross-prime CTL precursors.
1,774 citations
TL;DR: The TNFRp55 function renders mice resistant to lethal dosages of either lipopolysaccharides or S. aureus enterotoxin B, and the 55 kd TNFR plays a decisive role in the host's defense against microorganisms and their pathogenic factors.
1,762 citations
TL;DR: Results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory and show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses to reinfection.
Abstract: Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4−/− hosts, whereas memory CD8 cells generated in CD4−/− mice mounted defective recall responses in CD4+/+ adoptive hosts. These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory.
1,482 citations