Effect of murine recombinant interferon-γ in the protection of mice against salmonella

Matsumura, Haruo; Onozuka, Kazuyasu; Terada, Yasuhiko; Nakano, Yasunobu; Nakano, Masayasu

doi:10.1016/0192-0561(90)90067-w

Cited by 38 publications

(16 citation statements)

References 23 publications

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“…This effect was 66-fold increased due to liposomal encapsulation. An increased resistance due to administration of IFN-y against various bacterial infections was also found by other investigators [12,13,32]. However, the reports about the effects of administration of IFN-y on resistance against L. monoo, togenes infection show great discrepancy [14,15,17,18].…”

Section: Discussionmentioning

confidence: 72%

“…IFN-y stimulates macrophages to increased production of enzymes, monokines as well as enhanced tumoricidal activity [10,11]. In addition, it is shown that IFN-y increased the antibacterial defenses against several infections [12,13]. With respect to L. monocytogenes again the reports about the efficacy of IFN-y in stimulating host defenses are contradictory [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) in experimental infection with Listeria Monocytogenes

et al. 1993

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The effect of free and liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) on the resistance against Listeria monocytogenes infection in mice was investigated. It was shown that administration of MTPPE or IFN-y at 24 h before bacterial inoculation led to increased resistance against L. monocytogenes infection in terms of a decrease in bacterial numbers in liver and spleen. Encapsulation of MTPPE and IFN-y in liposomes increased their efficacy 33- or 66-fold, respectively. In addition, liposomal encapsulation led to a more rapid decrease in bacterial numbers. The immunomodulator to lipid ratio appeared to be very important in the antibacterial effect of LE-MTPPE and LE-IFN-y. When nontherapeutic doses of liposome-encapsulated MTPPE or IFN-y were administered in a larger amount of lipid (so at higher lipid: immunomodulator ratio), these doses became effective. Exposure of macrophages in monolayer infected with L. monocytogenes in vitro to MTPPE had no effect, whereas exposure to IFN-y only led to growth inhibition of the intracellular bacteria. However, incubation of macrophages with a combination of MTPPE and IFN-y resulted in killing of the intracellular bacteria. Exposure of macrophages in vivo to both immunomodulators in combination can be effected by using liposomes as carriers. It was observed that administration of MTPPE and IFN-y co-encapsulated in liposomes resulted in a synergistic enhanced antibacterial resistance against L. monocytogenes. Both reactive oxygen and nitrogen intermediates seemed to play a role in the killing of L. monocytogenes by macrophages activated with a combination of MTPPE and IFN-y.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) in experimental infection with Listeria Monocytogenes

et al. 1993

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“…Specifically, in mononuclear phagocytes infected with Salmonella enterica serovar typhimurium (S. typhimurium), IFN-c promotes the internalization of bacteria and stimulates their elimination by various mechanisms including reactive oxygen and nitrogen species (ROS and RNS), generated via NADPH phagocyte oxidase and iNOS, respectively [2][3][4][5]. In Salmonella-infected mice, treatment with recombinant IFN-c increases host survival and decreases bacterial numbers in liver and spleen [6]. Conversely, neutralization of murine IFN-c functions with specific antibodies results in reduced host survival and increased bacterial counts [7].…”

Section: Introductionmentioning

confidence: 99%

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

et al. 2008

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In stimulating effector functions of mononuclear phagocytes, IFN-c is of pivotal importance in host defense against intramacrophage pathogens including salmonellae. As the activity of IFN-c is modulated by iron and since a sufficient availability of iron is essential for the growth of pathogens, we investigated the regulatory effects of IFN-c on iron homeostasis and immune function in murine macrophages infected with Salmonella typhimurium. In Salmonella-infected phagocytes, IFN-c caused a significant reduction of iron uptake via transferrin receptor 1 and resulted in an increased iron efflux caused by an enhanced expression of the iron exporter ferroportin 1. Moreover, the expression of haem oxygenase 1 and of the siderophore-capturing antimicrobial peptide lipocalin 2 was markedly elevated following bacterial invasion, with IFN-c exerting a super-inducing effect. This observed regulatory impact of IFN-c reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed Salmonella typhimurium while concomitantly promoting NO and TNF-a production. Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-c concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. These regulations are thus consistent with the principles of nutritional immunity. IntroductionHost defense against intracellular microbes such as salmonellae or mycobacteria strongly depends on cell-mediated immunity, a major component of which is characterized by interactions between Th1 cells and macrophages [1]. By secreting Th1 cytokines, particularly IFN-c, antigen-specific Th1 cells activate a plethora of microbicidal mechanisms in infected macrophages. Specifically, in mononuclear phagocytes infected with Salmonella enterica serovar typhimurium (S. typhimurium), IFN-c promotes the internalization of bacteria and stimulates their elimination by various mechanisms including reactive oxygen and nitrogen species (ROS and RNS), generated via NADPH phagocyte oxidase and iNOS, respectively [2][3][4][5]. In Salmonella-infected mice, treatment with recombinant IFN-c increases host survival and decreases bacterial numbers in liver and spleen [6]. Conversely, neutralization of murine IFN-c functions with specific antibodies results in reduced host survival and increased bacterial counts [7]. Eur. J. Immunol. 2008. 38: 1923-1936 Immunity to infection In humans, the central importance of IFN-c for immune response against salmonellae is highlighted by the fact that patients with genetic defects in the IL-12-induced production of IFN-c or in the IFN-c receptor 1 selectively suffer from infections with salmonellae and otherwise weakly pathogenic mycobacteria since their phagocytes fail to eliminate these microbes [8,9]. Iron serves as an essential nutrient for nearly all pathogenic microorganisms, and the expression of iron acquisition systems by infectious agents is associated with their virule...

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“…It was shown that interferon gamma production was doubled in the presence of ASA [5]. Interferon gamma increases the antibacterial [19,20] and antiprotozoal defense mechanism against several infections [21,22]. The reports concerning the efficacy of interferon gamma in stimulating host defense mechanisms in L. monocytogenes infection are contradictory [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Influence of acetylsalicylic acid on aListeria monocytogenes infection

et al. 1993

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The influence of acetylsalicylic acid (ASA, CAS 50-78-2) on the Listeria monocytogenes infection in balb/c mice was investigated. One day prior to lethal or sublethal infection, balb/c mice were treated intravenously with therapeutic concentrations of ASA alone or ASA in combination with murine recombinant interferon gamma, a lymphokine produced by T-helper cells. Three days post-infection, parasite burdens of spleen and liver were determined by the colony-forming unit assay. It was shown that the prophylactic application of ASA in a concentration of 5 mg/kg body weight resulted in a more than 10-fold reduction of viable Listeria monocytogenes in spleen and liver of balb/c mice. In addition, the combination of a suboptimal dosage of interferon gamma with ASA resulted in a significantly higher survival rate compared to the untreated controls.

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Effect of murine recombinant interferon-γ in the protection of mice against salmonella

Cited by 38 publications

References 23 publications

Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) in experimental infection with Listeria Monocytogenes

Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) in experimental infection with Listeria Monocytogenes

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

Influence of acetylsalicylic acid on aListeria monocytogenes infection

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