Cytokines and the host defense against Listeria monocytogenes and Salmonella typhimurium

Langermans, Jan A. M.; Furth, R. van

doi:10.1007/978-94-011-0233-9_4

Cited by 7 publications

(7 citation statements)

References 105 publications

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“…Similar protective effect of several different cytokines against a wide range of bacterial infections has been reported [4,7,21,27,37,42,44,57,60,63]. The critical role of cytokines in infections with intracellual bacteria, like Listeria and Mycobacteria has been especially underlined by several groups and been recently reviewed in this journal [ 12,39]. Most of these studies underline the importance of the interaction between the various cytokines, which is extremely complicated and for the time being there are too many unknown factors to allow definite conclusions.…”

Section: Salmonella Typhimurium Infectionsupporting

confidence: 62%

Cytokines and bacterial infections

Degré

1996

Biotherapy

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During the recent 10-15 years a growing amount of knowledge has been accumulated on the role of cytokines in the pathogenesis and resistance to infections caused by nonviral agents, including a wide range of bacteria. Cytokines can be major mediators of the pathogenic effect in some diseases, and represent important defense mechanisms in others. Detailed knowledge on the role of the growing number of recognised cytokines is important, because it may represent means to combat and to prevent diseases caused by such infections.

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Section: Salmonella Typhimurium Infectionsupporting

confidence: 62%

Cytokines and bacterial infections

Degré

1996

Biotherapy

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“…Ϫ/Ϫ macrophages Engulfment of blood-borne bacteria and subsequent intracellular killing by cytokine-activated macrophages is a key defense mechanism during the early phase of listeriosis, restricting bacterial replication rate before the establishment of a specific and sterilizing T cell response (36). To test whether phagocytic activity depended on functional MK2, we determined the uptake of fluorescencelabeled E. coli particles by BMDM in an optimized quantitative phagocytosis assay.…”

Section: Diminished Phagocytosis Of Mk2mentioning

confidence: 99%

Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficient Mice Show Increased Susceptibility to Listeria monocytogenes Infection

Lehner

Schwoebel

Kotlyarov

et al. 2002

The Journal of Immunology

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Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of several kinases activated through direct phosphorylation by p38 mitogen-activated protein kinase. MK2 regulates LPS-induced TNF mRNA translation, and targeted mutation of the MK2 gene renders mice more resistant to d-galactosamine plus LPS-induced liver damage. In the present study, we investigated the role of MK2 in immune defense against Listeria monocytogenes infection. MK2-deficient mice displayed diminished resistance to L. monocytogenes due to impaired control of bacterial growth. The increase in bacterial load in MK2−/− mice was associated with normal levels of IL-1β, IL-6, and IFN-γ, whereas TNF production was strongly attenuated. In line, MK2-deficient bone marrow-derived macrophages showed impaired release of TNF, but not of IL-1β, in response to various bacterial stimuli in addition to decreased phagocytosis of fluorescence-labeled bacteria. Furthermore, spleen cells from MK2−/− mice displayed diminished IFN-γ synthesis after stimulation with L. monocytogenes. In contrast, MK2 deficiency had no effect on macrophage generation of NO or on oxidative burst activity in response to L. moocytogenes. These results indicate an essential role of MK2 in host defense against intracellular bacteria probably via regulation of TNF and IFN-γ production required for activation of antibacterial effector mechanisms.

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“…(ii) Efficient host defense against serovar Typhimurium depends on the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-␣) and gamma interferon (IFN-␥) and susceptibility is increased by neutralization of these mediators (reviewed in reference 25). If endotoxin tolerance has a negative impact on host defense, e.g., by impairing bacterially induced cytokine release, this should be most obvious during infection with this gram-negative pathogen.…”

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confidence: 99%

Improved Innate Immunity of Endotoxin-Tolerant Mice Increases Resistance toSalmonella entericaSerovar Typhimurium Infection despite Attenuated Cytokine Response

Lehner

Ittner

Bundschuh³

et al. 2001

Infect Immun

109

100

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During infection with gram-negative bacteria, exposure of immune cells to lipopolysaccharide (LPS) from the bacterial cell membrane induces a rapid cytokine response which is essential for the activation of host defenses against the invading pathogens. Administration of LPS to mice induces a state of hyporesponsiveness, or tolerance, characterized by reduced cytokine production upon subsequent LPS challenge. In the model of experimental Salmonella enterica serovar Typhimurium infection of mice, we assessed the question of whether complete LPS tolerance induced by repetitive doses of LPS interfered with cytokine production and host defense against gram-negative bacteria. Although production of various cytokines in response to serovar Typhimurium was attenuated by LPS pretreatment, LPS-tolerant mice showed improved antibacterial activity, evidenced by a prolongation of survival and a continuously lower bacterial load. We attribute this protective effect to three independent mechanisms. (i) Peritoneal accumulation of leukocytes in the course of LPS pretreatment accounted for enhanced defense against serovar Typhimurium during the first 6 h of infection but not for decreased bacterial load in late-stage infection. (ii) LPS-tolerant mice had an increased capacity to recruit neutrophilic granulocytes during infection. (iii) LPS-tolerant mice showed threefold-increased Kupffer cell numbers, enhanced phagocytic activity of the liver, and strongly improved clearance of blood-borne serovar Typhimurium. These results demonstrate that despite attenuated cytokine response, acquired LPS tolerance is associated with enhanced resistance to infections by gram-negative bacteria and that this effect is mainly mediated by improved effector functions of the innate immune system. Endotoxin, or lipopolysaccharide (LPS), a glycolipid of the cell membranes of gram-negative bacteria, is one of the most potent stimulators of immune responses known. The immune system responds to LPS with a systemic production of proinflammatory cytokines, which recruit and activate immune cells to eliminate invading pathogens (40). Although these cytokines are indispensible for the efficient control of the growth and dissemination of the pathogen (7,10,17), an excessive inflammatory response is potentially autodestructive and may lead to microcirculatory dysfunction, causing tissue damage, septic shock, and eventually death (3, 14). The phenomenon of endotoxin tolerance is known from animal models of "sterile infection" induced by LPS: after an initial low dose of LPS, animals are protected against the detrimental consequences of a subsequent high dose of LPS. This protection is associated with an attenuated cytokine response to LPS (11) due to a downregulation of macrophage responsiveness (12).The value of endotoxin tolerance induction as a mean of sepsis prophylaxis was studied in animal models of endotoxic shock or polymicrobial sepsis. In these models, protection by tolerance induction was ascribed to the decreased proinflammatory response, resulting i...

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Cytokines and the host defense against Listeria monocytogenes and Salmonella typhimurium

Cited by 7 publications

References 105 publications

Cytokines and bacterial infections

Cytokines and bacterial infections

Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficient Mice Show Increased Susceptibility to Listeria monocytogenes Infection

Improved Innate Immunity of Endotoxin-Tolerant Mice Increases Resistance toSalmonella entericaSerovar Typhimurium Infection despite Attenuated Cytokine Response

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