Interferon-gamma-induced activation of indoleamine 2,3-dioxygenase in cord blood monocyte-derived macrophages inhibits the growth of group B streptococci.
Neonatal sepsis is most often caused by group B streptococci (GBS) and is a major cause of death in the neonatal period. The response of the immune system in the newborn child has received much attention and is thought to be deficient in a number of ways. The effector response of neonatal monocyte-derived macrophages (MDM) was investigated. Interferon-gamma induced the activation of indoleamine 2,3-dioxygenase in MDM and inhibited the growth of GBS. Both effects were enhanced by the addition of tumor necrosis factor-alpha to the culture conditions. The coincident supplementation of L-tryptophan with the bacteria abrogated the bacterial growth inhibition, thus confirming the causative role of L-tryptophan depletion. Control of the extracellular as well as intracellular L-tryptophan levels may thus be one of the effector mechanisms with which the immune system defends the host against GBS dissemination and disease.
MacKenzie
C R
CR
Institute for Medical Microbiology and Virology, Heinrich-Heine-University, Düsseldorf, Germany. Colin.Mackenzie@uni-duesseldorf.de
Hadding
U
U
Däubener
W
W
D002478:Cells, Cultured; D004789:Enzyme Activation; D005312:Fetal Blood; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000382:microbiology*; D009000:Monocytes; D013292:Streptococcus agalactiae / Q000254:growth & development*; D014366:Tryptophan Oxygenase / Q000097:blood / Q000378:metabolism*
D007371:Interferon-gamma; D014366:Tryptophan Oxygenase