TY - JOUR
T1 - Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection
AU - Divanovic, Senad
AU - Sawtell, Nancy M.
AU - Trompette, Aurelien
AU - Warning, Jamie I.
AU - Dias, Alexandra
AU - Cooper, Andrea M.
AU - Yap, George S.
AU - Arditi, Moshe
AU - Shimada, Kenichi
AU - Duhadaway, James B.
AU - Prendergast, George C.
AU - Basaraba, Randall J.
AU - Mellor, Andrew L.
AU - Munn, David H.
AU - Aliberti, Julio
AU - Karp, Christopher L.
N1 - Funding Information:
Financial support. This work was supported by grants from the National Institute of Allergy and Infectious Disease to C. L. K. (AI057992), A. L. M. (AI063402), and N. M. S. (AI032121); the National Institute of Child Health and Development to A. L. M. (HD041187); the National Cancer Institute to D. L. M. (CA096651, CA103320, CA112431); and the National Institute of Arthritis and Musculoskeletal and Skin Diseases to S. D. (AR007594).
PY - 2012/1/1
Y1 - 2012/1/1
N2 - Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role-antimicrobial or immunoregulatory-is pathogen-specific.
AB - Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role-antimicrobial or immunoregulatory-is pathogen-specific.
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U2 - 10.1093/infdis/jir621
DO - 10.1093/infdis/jir621
M3 - Article
C2 - 21990421
AN - SCOPUS:84555187508
SN - 0022-1899
VL - 205
SP - 152
EP - 161
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -
