IFN-GAMMA-MEDIATED ANTIMICROBIAL RESPONSE - INDOLEAMINE 2,3-DIOXYGENASE-DEFICIENT MUTANT HOST-CELLS NO LONGER INHIBIT INTRACELLULAR CHLAMYDIA SPP OR TOXOPLASMA GROWTH

The role of indoleamine 2,3-dioxygenase (IDO) in IFN-gamma-mediated in hibition of intracellular parasite growth has been examined previously , although earlier work has been largely correlative. In this study, w e defined more completely the role of IDO in the IFN- antimicrobial re sponse. Two mutant cell lines, derived from ME180 cells and exhibiting reduced IDO activity (IR3B6A, IR3B6B) were characterized to determine if they retained the capacity to inhibit intracellular Chlamydia and Toxoplasma growth. Mutant cells treated with IFN-gamma exhibited reduc ed capacity to suppress pathogen growth. The expression of several IFN -regulated genes also was measured to confirm that the inability to in hibit pathogen growth was because of the lack of IDO. The expression o f class II MHC, intracellular adhesion molecule-1, MxA, and P68 kinase genes was induced in the IFN-gamma-treated wild type ME1 80 cells, bu t was variable in the mutant cell lines, supporting the hypothesis tha t IFN-gamma-induced production of IDO is a key IFN-gamma-mediated anti microbial mechanism.