Regulation of Ido-Mediated Bacteriostasis In Macrophages: Role of Antibiotics And Anti-Inflammatory Agents

MacKenzie, Colin R.; Worku, Daniel; Däubener, Walter

doi:10.1007/978-1-4615-0135-0_7

Cited by 10 publications

(10 citation statements)

References 10 publications

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“…IDO activity has been recognized as one of the major response elements during infection of mammalian cells with a large variety of pathogens, including Gram‐positive and Gram‐negative bacteria, viruses and parasites such as Toxoplasma gondii and Leishmania donovani (Bortolotti et al, ; Dai, Pan, Kwok, & Dubey, ; Dӓubener & MacKenzie, ; Narui et al, ; Niño‐Castro et al, ; Pfefferkorn, ; Plain et al, ). The increase in IDO activity has been documented both in animals and in human in the course of different diseases (chronic lung inflammation in pigs, human streptococcal infection and toxic‐shock‐like syndrome [STSS]) (Dӓubener & MacKenzie, ; MacKenzie, Worku, & Dӓubener, ; Melchior, Sève, & Le Floc‘h, ; Murr, Gerlach, Widner, Dierich, & Fuchs, ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, TNF‐alfa enhances IFN‐gamma induced IDO activity and antimicrobial effect in human glioblastoma cells, whereas both IFN‐gamma mediated effects were blocked by TNF‐alfa as well as by IL‐1 in a human uroepithelial cell line (Dӓubener & MacKenzie, ). In addition, it has been shown that IDO‐mediated bacteriostasis can be inhibited both by antihuman IFN‐gamma antibodies (Murr et al, ) and by the cytokines IL‐10, IL‐4 and TGFβ (MacKenzie et al, ). Therefore, it is likely that the IDO antibacterial activity also depends on the inflammation phase.…”

Section: Discussionmentioning

confidence: 99%

“…The increase in IDO activity has been documented both in animals and in human in the course of different diseases (chronic lung inflammation in pigs, human streptococcal infection and toxic-shocklike syndrome [STSS]) (Dӓubener & MacKenzie, 1999;MacKenzie, Worku, & Dӓubener, 2003;Melchior, Sève, & Le Floc'h, 2004;Murr, Gerlach, Widner, Dierich, & Fuchs, 2001).…”

Section: Discussionmentioning

confidence: 99%

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Tryptophan, kynurenine, kynurenic acid concentrations and indoleamine 2,3‐dioxygenase activity in serum and milk of dairy cows with subclinical mastitis caused by coagulase‐negative staphylococci

Bochniarz

Kocki

Dąbrowski

et al. 2018

Reprod Domestic Animals

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The aim of the study was to investigate serum and milk concentrations of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and indoleamine 2,3-dioxygenase (IDO) activity in cows suffering from subclinical mastitis caused by coagulase-negative staphylococci (MSCNS). TRP and kynurenines were determined by high-performance liquid chromatography (HPLC), and IDO activity was calculated as the KYN/TRP ratio. The blood and milk samples were collected from 40 midlactation Holstein-Fresian cows from two herds in the Lublin region in Poland. In the milk samples from 20 cows with subclinical mastitis, coagulase-negative staphylococci were isolated and in the milk obtained from healthy cows growth of microorganisms was not detected. TRP, KYN and KYNA concentrations were significantly lower in milk of cows with MSCNS compared to control animals (4.47 vs. 7.24 µM, 0.14 vs. 0.21 µM, 1.58 vs. 2.18 nM, respectively). There was no statistically significant difference in TRP and KYNA concentrations in serum between the studied animal groups (32.97 vs. 39.29 µM, 31.3 vs. 26.5 nM, respectively). In turn, the level of KYN was lower in the serum (0.81 vs. 1.13 µM) of cows with mastitis compared to healthy ones. No statistically significant differences in IDO activity, both in serum and in milk (25.24 and 27.55, 28.56 and 27.17, respectively) was revealed between the studied groups. These findings may have potential implications for diagnosis of mastitis in cows because reduction of these parameters in milk might be a marker predicting the occurrence of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Tryptophan, kynurenine, kynurenic acid concentrations and indoleamine 2,3‐dioxygenase activity in serum and milk of dairy cows with subclinical mastitis caused by coagulase‐negative staphylococci

Bochniarz

Kocki

Dąbrowski

et al. 2018

Reprod Domestic Animals

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“…Interestingly, both immune and behavioral regulatory systems [20]–[24] as well as bacterial growth [25], [26] depend on the availability of tryptophan (Trp). Under basal conditions in mammals, Trp catabolism is mediated by tryptophan dioxygenase (TDO) activation - mainly in the liver - which is controlled by GCs [22], [27].…”

Section: Introductionmentioning

confidence: 99%

Psychological Stress-Induced, IDO1-Dependent Tryptophan Catabolism: Implications on Immunosuppression in Mice and Humans

et al. 2010

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It is increasingly recognized that psychological stress influences inflammatory responses and mood. Here, we investigated whether psychological stress (combined acoustic and restraint stress) activates the tryptophan (Trp) catabolizing enzyme indoleamine 2,3-dioxygenase 1(IDO1) and thereby alters the immune homeostasis and behavior in mice. We measured IDO1 mRNA expression and plasma levels of Trp catabolites after a single 2-h stress session and in repeatedly stressed (4.5-days stress, 2-h twice a day) naïve BALB/c mice. A role of cytokines in acute stress-induced IDO1 activation was studied after IFNγ and TNFα blockade and in IDO1−/− mice. RU486 and 1-Methyl-L-tryptophan (1-MT) were used to study role of glucocorticoids and IDO1 on Trp depletion in altering the immune and behavioral response in repeatedly stressed animals. Clinical relevance was addressed by analyzing IDO1 activity in patients expecting abdominal surgery. Acute stress increased the IDO1 mRNA expression in brain, lung, spleen and Peyer's patches (max. 14.1±4.9-fold in brain 6-h after stress) and resulted in a transient depletion of Trp (−25.2±6.6%) and serotonin (−27.3±4.6%) from the plasma measured 6-h after stress while kynurenine levels increased 6-h later (11.2±9.3%). IDO1 mRNA up-regulation was blocked by anti-TNFα and anti-IFNγ treatment. Continuous IDO1 blockade by 1-MT but not RU486 treatment normalized the anti-bacterial defense and attenuated increased IL-10 inducibility in splenocytes after repeated stress as it reduced the loss of body weight and behavioral alterations. Moreover, kynurenic acid which remained increased in 1-MT treated repeatedly stressed mice was identified to reduce the TNFα inducibility of splenocytes in vitro and in vivo. Thus, psychological stress stimulates cytokine-driven IDO1 activation and Trp depletion which seems to have a central role for developing stress-induced immunosuppression and behavioral alteration. Since patients showed Trp catabolism already prior to surgery, IDO is also a possible target enzyme for humans modulating immune homeostasis and mood.

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“…The antimicrobial effect of IDO was shown to be under strict control by the immune system. In vitro experiments revealed IDO-dependent bacteriostasis of Staphylococcus aureus and group A Streptococcus to be inhibited by cytokines IL-10, IL-4, and TGF-as well as by the addition of the anti-inflammatory agent indomethacin [20], which could be of relevance for pharmacological intervention after HSCT.…”

Section: Ido-mediated Modulation Of Inflammatory Processes After Hsctmentioning

confidence: 98%

Indoleamine 2,3-Dioxygenase in Hematopoietic Stem Cell Transplantation

Hainz

Jürgens²,

Wekerle³

et al. 2007

CDM

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Hematopoietic stem cell transplantation (HSCT) is complicated by unwelcome side-effects that arise on the basis of an altered immune system. Infectious complications and alloreactive T-cell responses trigger a process of ongoing immune activation and inflammation. Negative-feedback mechanisms to counteract inflammation involve the induction of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO), which mediates anti-inflammatory activities and T-cell inhibition via tryptophan catabolism. However, persistent immune activation and generalized release of pro-inflammatory cytokines deviate immune regulation towards chronic suppression incapable to abrogate the inflammatory response. This review focuses on the unique role of tryptophan catabolism in modulating inflammatory processes and T-cell responses after HSCT.

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Regulation of Ido-Mediated Bacteriostasis In Macrophages: Role of Antibiotics And Anti-Inflammatory Agents

Cited by 10 publications

References 10 publications

Tryptophan, kynurenine, kynurenic acid concentrations and indoleamine 2,3‐dioxygenase activity in serum and milk of dairy cows with subclinical mastitis caused by coagulase‐negative staphylococci

Tryptophan, kynurenine, kynurenic acid concentrations and indoleamine 2,3‐dioxygenase activity in serum and milk of dairy cows with subclinical mastitis caused by coagulase‐negative staphylococci

Psychological Stress-Induced, IDO1-Dependent Tryptophan Catabolism: Implications on Immunosuppression in Mice and Humans

Indoleamine 2,3-Dioxygenase in Hematopoietic Stem Cell Transplantation

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