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Published on: October 3, 2018
A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection.
M C Heller1, C P Drew, K A Jackson
1Dept. of Veterinary Medicine and Epidemiology, University of California Davis, One Shields Ave., Davis, CA 95616, USA. mcheller@ucdavis.edu
Indoleamine 2,3-dioxygenase (IDO) dampens inflammation during Rhodococcus equi infection by reducing regulatory T cells. IDO deficiency in mice led to increased liver inflammation and decreased TGFβ and FOXP3 expression.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Rhodococcus equi is a pathogen affecting foals and immunocompromised individuals.
- The bacterium infects macrophages and dendritic cells (DC).
- Indoleamine 2,3-dioxygenase (IDO) is upregulated during R. equi infection.
Purpose of the Study:
- To assess the role of IDO in R. equi infection.
- To investigate the immune-regulatory function of IDO in R. equi pathogenesis.
Main Methods:
- Assessed R. equi growth requirement for tryptophan.
- Inhibited IDO pharmacologically in equine macrophages.
- Infected IDO-deficient and control mice with R. equi.
- Analyzed bacterial counts, inflammation scores, and gene expression (IFNγ, TNFα, IL-4, IL-6, IL-10, IL-12, IL-23, FoxP3, TGFβ).
Main Results:
- R. equi growth did not require tryptophan; IDO inhibition did not affect intracellular proliferation.
- IDO-deficient mice showed no difference in bacterial load but had higher liver inflammation at 6 days post-infection.
- IDO deficiency led to decreased TGFβ and FOXP3 expression and fewer FOXP3+ regulatory T cells in the liver.
Conclusions:
- IDO expression by macrophages and DC dampens the inflammatory response to R. equi infection in mice.
- IDO plays a role in immune regulation during R. equi infection, potentially by influencing regulatory T cell populations.
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