Role Of Ido Activation In Anti-Microbial Defense in Human Native Astrocytes
Part of the
Advances in Experimental Medicine and Biology
book series (AEMB, volume 527)
The most serious complication of human toxoplasmosis is the development of toxoplasmic encephalitis. It is well established that in the brainToxoplasma gondiiis able to replicate in microglial cells, astrocytes and neurons, and that all three cell types can harbor toxoplasma cysts. The role of astrocytes in the defense against toxoplasma is not clear. The most prominent effector-mechanisms against toxoplasma are the induction of the inducible form of the nitric oxide synthase (iNOS), and the induction of indoleamine 2,3-dioxygenase (IDO).
In this paper we show that interferon (IFN)-y-activated, native human astrocytes express IDO activity, as shown by the detection of IDO mRNA using RT-PCR, detection of enzyme expression with IDO-specific monoclonal antibodies in Western blots, as well as by direct measurement of enzyme activity in the activated cells. IFN-y—mediated IDO activity in human astrocytes inhibits the growth ofToxoplasma gondiiand of group B streptococci. Furthermore, we show for the first time that IFN-y induced IDO activity is also effective in inhibiting the growth of Herpes Simplex Virus in astrocyte cultures.
In addition, iNOS expression was detectable by RT-PCR in all batches of astrocytes tested when stimulated with a cytokine cocktail of IFN-y, TNF-a, IL-1 and LPS. Furthermore, we found that the amount of nitric oxide produced by astrocytes is not sufficient to inhibit either toxoplasmal or bacterial growth. Co-activation of iNOS and IDO on the other hand, results in an inhibition of IDO activity in astrocytes.
KeywordsNitric Oxide Nitric Oxide Quinolinic Acid Astrocyte Culture Human Astrocyte
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