IL-4 and IL-13 regulate the induction of indoleamine 2,3-dioxygenase activity and the control of Toxoplasma gondii replication in human fibroblasts activated with IFN-gamma
Acl. Chaves et al., IL-4 and IL-13 regulate the induction of indoleamine 2,3-dioxygenase activity and the control of Toxoplasma gondii replication in human fibroblasts activated with IFN-gamma, EUR J IMMUN, 31(2), 2001, pp. 333-344
The ability of up-regulatory [recombinant (r) IFN-gamma, rIFN-beta and rTNf
-alpha] and down-regulatory (rIL-4, rIL-10 and rIL-13) cytokines to control
the expression of indoleamine 2,3-dioxygenase (INDO) and anti-Toxoplasma a
ctivity in the human fibrosarcoma cell line 2C4 was evaluated. Activation o
f fibroblasts with rIFN-gamma, rIFN-beta and rTNF-alpha resulted in augment
ation of INDO expression and activity leading to 40.0, 25.0 and 27.0 % inhi
bition of tachyzoite growth, respectively. An additive effect was observed
when host cells were incubated with rIFN-gamma plus rTNF-alpha. With regard
to the down-regulatory cytokines we observed that IL-4 as well as IL-13, b
ut not IL-10, induced significant inhibition of IFN-gamma -induced control
of parasite replication, INDO mRNA expression and tryptophan catabolism. Si
milarly, IL-4 but not IL-10 inhibited the cell surface expression of HLA-DR
and CD2 induced by IFN-gamma. Consistent with these findings we were able
to detect by reverse transcription-PCR the expression of mRNA for different
chains of IL-4 and IL-13 receptors (IL-4R alpha, IL-13R alpha1 and IL-13R
alpha2) but not for IL-10 receptor in the 2C4 and other human lung fibrobla
st cell lines (LL24 and MRC5). Together our results indicate that IL-4 and
IL-13, but not IL-10, are implicated in the negative regulation of IFN-gamm
a -induced anti-Toxoplasma activity in human cells from fibroblast lineage.