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New Insights into IDO Biology in Bacterial and Viral Infections.

Schmidt SV, Schultze JL - Front Immunol (2014)

Bottom Line: Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance.In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C.Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed.

View Article: PubMed Central - PubMed

Affiliation: Genomics and Immunoregulation, LIMES-Institute, University of Bonn , Bonn , Germany.

ABSTRACT
Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance. In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C. Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed. Here, we review these recent findings highlighting the central role of IDO and tryptophan metabolism in many major human infections. Moreover, we also shed light on issues concerning human-specific and mouse-specific host-pathogen interactions that need to be considered when studying the biology of IDO in the context of infections.

No MeSH data available.


Related in: MedlinePlus

IDO links chronic viral and bacterial infections to cases of depression. Underlying mechanisms of the connection between chronic infection with viruses or bacteria and the onset of mental disorders in men are unknown. Insufficient levels of serotonin in chronically infected and depressive patients are thought to be the consequence of constitutively elevated levels of IDO. Murine models of chronic infections are established to decipher the involvement of IDO in the development of depressive-like behavior.
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Figure 2: IDO links chronic viral and bacterial infections to cases of depression. Underlying mechanisms of the connection between chronic infection with viruses or bacteria and the onset of mental disorders in men are unknown. Insufficient levels of serotonin in chronically infected and depressive patients are thought to be the consequence of constitutively elevated levels of IDO. Murine models of chronic infections are established to decipher the involvement of IDO in the development of depressive-like behavior.

Mentions: An interesting link between chronic inflammatory diseases and neurological disorders has been recently made with IDO being involved. Patients suffering from chronic inflammatory diseases show often signs of depressive mood behavior (Figure 2). In patients with chronic HIV infection, the elevated Trp catabolism maintained by IDO expression is associated with reduced levels of free serum Trp (48, 49). This correlates with a reduction of serotonin (5-HT) and serotonin transporter (5-HTT) expression, as well as an accumulation of neurotoxic Trp metabolites (50). Especially, Kyn and quinolinic acid (QA) can be detected in cerebrospinal fluids of HIV patients and are linked to the development of neuropsychiatric disorders, as part of the Neuro-AIDS complex of symptoms (50). HIV-1 associated dementia (HAD) is correlated to IDO and Kyn induced by Tat of HIV-1 clade B in human primary astrocytes (51) while Tat of HIV-1 clade C does not induce IDO activity in human primary astrocytes and is not associated with HAD. Further evidence for the role of Tat for IDO expression in the brain came from experiments injecting Tat protein intracerebroventricularly into different mice strains. Further, when injecting Tat, induction of IDO and several other pro-inflammatory cytokines in the brain was associated with reduced mobility and depressive-like behavior (52), demonstrating the important role of IDO in the pathophysiology of HIV infection. Blockade of IDO or upstream events of IDO induction in chronic infection might be a novel approach to treat chronic HIV infections.


New Insights into IDO Biology in Bacterial and Viral Infections.

Schmidt SV, Schultze JL - Front Immunol (2014)

IDO links chronic viral and bacterial infections to cases of depression. Underlying mechanisms of the connection between chronic infection with viruses or bacteria and the onset of mental disorders in men are unknown. Insufficient levels of serotonin in chronically infected and depressive patients are thought to be the consequence of constitutively elevated levels of IDO. Murine models of chronic infections are established to decipher the involvement of IDO in the development of depressive-like behavior.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128074&req=5

Figure 2: IDO links chronic viral and bacterial infections to cases of depression. Underlying mechanisms of the connection between chronic infection with viruses or bacteria and the onset of mental disorders in men are unknown. Insufficient levels of serotonin in chronically infected and depressive patients are thought to be the consequence of constitutively elevated levels of IDO. Murine models of chronic infections are established to decipher the involvement of IDO in the development of depressive-like behavior.
Mentions: An interesting link between chronic inflammatory diseases and neurological disorders has been recently made with IDO being involved. Patients suffering from chronic inflammatory diseases show often signs of depressive mood behavior (Figure 2). In patients with chronic HIV infection, the elevated Trp catabolism maintained by IDO expression is associated with reduced levels of free serum Trp (48, 49). This correlates with a reduction of serotonin (5-HT) and serotonin transporter (5-HTT) expression, as well as an accumulation of neurotoxic Trp metabolites (50). Especially, Kyn and quinolinic acid (QA) can be detected in cerebrospinal fluids of HIV patients and are linked to the development of neuropsychiatric disorders, as part of the Neuro-AIDS complex of symptoms (50). HIV-1 associated dementia (HAD) is correlated to IDO and Kyn induced by Tat of HIV-1 clade B in human primary astrocytes (51) while Tat of HIV-1 clade C does not induce IDO activity in human primary astrocytes and is not associated with HAD. Further evidence for the role of Tat for IDO expression in the brain came from experiments injecting Tat protein intracerebroventricularly into different mice strains. Further, when injecting Tat, induction of IDO and several other pro-inflammatory cytokines in the brain was associated with reduced mobility and depressive-like behavior (52), demonstrating the important role of IDO in the pathophysiology of HIV infection. Blockade of IDO or upstream events of IDO induction in chronic infection might be a novel approach to treat chronic HIV infections.

Bottom Line: Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance.In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C.Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed.

View Article: PubMed Central - PubMed

Affiliation: Genomics and Immunoregulation, LIMES-Institute, University of Bonn , Bonn , Germany.

ABSTRACT
Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance. In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C. Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed. Here, we review these recent findings highlighting the central role of IDO and tryptophan metabolism in many major human infections. Moreover, we also shed light on issues concerning human-specific and mouse-specific host-pathogen interactions that need to be considered when studying the biology of IDO in the context of infections.

No MeSH data available.


Related in: MedlinePlus