Abstract
Rhodococcus equi is a facultative intracellular bacterial pathogen of foals and immunocompromised humans that infects and proliferates within host macrophages and dendritic cells (DC). Indoleamine 2,3-dioxygenase (IDO), the initial enzyme in the tryptophan catabolism pathway, is upregulated in R. equi infected equine monocyte-derived DC and alveolar macrophages. Tryptophan requirement of R. equi for extracellular and intracellular growth was assessed. Growth of R. equi in minimal media did not require tryptophan and pharmacologic inhibition of IDO had no effect on intracellular proliferation of R. equi in equine alveolar macrophages. To investigate an immune-regulatory role for INDO in R. equi infection, IDO-/- (B6.129-Indotm1Alm/J) (n=22) and strain matched control (C57BL/6J) (n=20) mice were infected with R. equi by intraperitoneal injection, for 3 and 6 days. There was no difference in bacterial counts in liver or spleen between the two groups. Histological sections of liver and spleen were assigned inflammation scores and RT-PCR for interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα), IL-4, IL-6, IL-10, IL-12, IL-23, forkhead box P3 (FoxP3), and transforming growth factor-beta (TGFβ) was performed on liver and spleen. Liver tissue of IDO-/- had higher inflammation scores at 6 days post-infection (PI) (P=0.05) and had decreased expression of TGFβ at 3 days PI (P=0.01), and FOXP3 at 3 days (P=0.02) and 6 days (P=0.03) compared to control mice. Immunostaining for FOXP3 showed lower numbers of FOXP3+ regulatory T cells in liver of IDO-/- mice 6 days PI. Prolonged inflammation in the liver tissue of IDO-/- mice corresponded with lower expression of FOXP3 and TGFβ in that tissue, and also with lower numbers of FOXP3+ regulatory T cells. We conclude that IDO expression by activated macrophages and DC plays a role in dampening the inflammatory response to R. equi infection in mice.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 174-182 |
| Number of pages | 9 |
| Journal | Veterinary Immunology and Immunopathology |
| Volume | 138 |
| Issue number | 3 |
| DOIs | |
| State | Published - Dec 1 2010 |
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Keywords
- Equine immune response
- FOXP3
- Indoleamine 2,3-dioxygenase
- Regulatory T cells
- Rhodococcus equi
ASJC Scopus subject areas
- Immunology
- veterinary(all)
Cite this
A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection. / Heller, Meera C; Drew, C. P.; Jackson, K. A.; Griffey, Stephen M; Watson, Johanna L.
In: Veterinary Immunology and Immunopathology, Vol. 138, No. 3, 01.12.2010, p. 174-182.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection
AU - Heller, Meera C
AU - Drew, C. P.
AU - Jackson, K. A.
AU - Griffey, Stephen M
AU - Watson, Johanna L
PY - 2010/12/1
Y1 - 2010/12/1
N2 - Rhodococcus equi is a facultative intracellular bacterial pathogen of foals and immunocompromised humans that infects and proliferates within host macrophages and dendritic cells (DC). Indoleamine 2,3-dioxygenase (IDO), the initial enzyme in the tryptophan catabolism pathway, is upregulated in R. equi infected equine monocyte-derived DC and alveolar macrophages. Tryptophan requirement of R. equi for extracellular and intracellular growth was assessed. Growth of R. equi in minimal media did not require tryptophan and pharmacologic inhibition of IDO had no effect on intracellular proliferation of R. equi in equine alveolar macrophages. To investigate an immune-regulatory role for INDO in R. equi infection, IDO-/- (B6.129-Indotm1Alm/J) (n=22) and strain matched control (C57BL/6J) (n=20) mice were infected with R. equi by intraperitoneal injection, for 3 and 6 days. There was no difference in bacterial counts in liver or spleen between the two groups. Histological sections of liver and spleen were assigned inflammation scores and RT-PCR for interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα), IL-4, IL-6, IL-10, IL-12, IL-23, forkhead box P3 (FoxP3), and transforming growth factor-beta (TGFβ) was performed on liver and spleen. Liver tissue of IDO-/- had higher inflammation scores at 6 days post-infection (PI) (P=0.05) and had decreased expression of TGFβ at 3 days PI (P=0.01), and FOXP3 at 3 days (P=0.02) and 6 days (P=0.03) compared to control mice. Immunostaining for FOXP3 showed lower numbers of FOXP3+ regulatory T cells in liver of IDO-/- mice 6 days PI. Prolonged inflammation in the liver tissue of IDO-/- mice corresponded with lower expression of FOXP3 and TGFβ in that tissue, and also with lower numbers of FOXP3+ regulatory T cells. We conclude that IDO expression by activated macrophages and DC plays a role in dampening the inflammatory response to R. equi infection in mice.
AB - Rhodococcus equi is a facultative intracellular bacterial pathogen of foals and immunocompromised humans that infects and proliferates within host macrophages and dendritic cells (DC). Indoleamine 2,3-dioxygenase (IDO), the initial enzyme in the tryptophan catabolism pathway, is upregulated in R. equi infected equine monocyte-derived DC and alveolar macrophages. Tryptophan requirement of R. equi for extracellular and intracellular growth was assessed. Growth of R. equi in minimal media did not require tryptophan and pharmacologic inhibition of IDO had no effect on intracellular proliferation of R. equi in equine alveolar macrophages. To investigate an immune-regulatory role for INDO in R. equi infection, IDO-/- (B6.129-Indotm1Alm/J) (n=22) and strain matched control (C57BL/6J) (n=20) mice were infected with R. equi by intraperitoneal injection, for 3 and 6 days. There was no difference in bacterial counts in liver or spleen between the two groups. Histological sections of liver and spleen were assigned inflammation scores and RT-PCR for interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα), IL-4, IL-6, IL-10, IL-12, IL-23, forkhead box P3 (FoxP3), and transforming growth factor-beta (TGFβ) was performed on liver and spleen. Liver tissue of IDO-/- had higher inflammation scores at 6 days post-infection (PI) (P=0.05) and had decreased expression of TGFβ at 3 days PI (P=0.01), and FOXP3 at 3 days (P=0.02) and 6 days (P=0.03) compared to control mice. Immunostaining for FOXP3 showed lower numbers of FOXP3+ regulatory T cells in liver of IDO-/- mice 6 days PI. Prolonged inflammation in the liver tissue of IDO-/- mice corresponded with lower expression of FOXP3 and TGFβ in that tissue, and also with lower numbers of FOXP3+ regulatory T cells. We conclude that IDO expression by activated macrophages and DC plays a role in dampening the inflammatory response to R. equi infection in mice.
KW - Equine immune response
KW - FOXP3
KW - Indoleamine 2,3-dioxygenase
KW - Regulatory T cells
KW - Rhodococcus equi
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U2 - 10.1016/j.vetimm.2010.07.013
DO - 10.1016/j.vetimm.2010.07.013
M3 - Article
VL - 138
SP - 174
EP - 182
JO - Veterinary Immunology and Immunopathology
JF - Veterinary Immunology and Immunopathology
SN - 0165-2427
IS - 3
ER -