STAT1 Is Essential for Antimicrobial Effector Function but Dispensable for Gamma Interferon Production duringToxoplasma gondiiInfection

Transcriptional control of human T‐BET expression: The role of Sp1

“…Work regarding the regulation of the T-bet gene itself has been limited; we know it is positively regulated by the Notch1 transcription factor and by proinflammatory cytokines such as IL-12, IL-15 and IL-18 [1,3,4,14,15] and IFN-c [17], and negatively regulated by TGF-b [14,15,20]. Studies of the transcription factors activated by these cytokines suggest that STAT4-, STAT1-and SMADdependent and -independent mechanisms are likely involved in the regulation of T-bet [5,8,[14][15][16][18][19][20][21], but definitive characterizations of these and other potential regulatory pathways have not been reported.…”

“…This suggests that STAT may play a role in the regulation of this gene; however, the regulation of T-bet has been reported as both STAT4 dependent and STAT4 independent [5,7,16]. T-bet induces IFN-c that in turn positively regulates T-bet expression [17], but there is no consistent conclusion on whether the regulation is or is not mediated by STAT1 [5,8,16,18,19]. The anti-inflammatory cytokine TGF-b 1 has previously been shown to down-regulate T-bet [14,15,20], and in some but not all instances this is mediated by SMAD proteins [21].…”

CD40, autophagy and Toxoplasma gondii

“…Children with an autosomal dominant defect in IFN-γR1 that causes a deletion in the STAT1 binding site do not develop disease when infected with T. gondii (Janssen et al 2002). In marked contrast, STAT1 -/-mice die within one week after infection with the parasite (Gavrielescu et al 2004, Lieberman et al 2004. The differences between the immune response in humans and mice also apply to the downstream effectors of IFN-γ.…”

“…This possibility is particularly relevant to humans because of their restricted expression of NOS2 and because patients with a mutation in IFN-γR1 that prevents recruitment of STAT1 do not develop disease after T. gondii infection while STAT1 -/-mice die acutely after challenge with the parasite (Janssen et al 2002, Gavrielescu et al 2004, Lieberman et al 2004.…”

Roles of Toxoplasma gondii‐Derived Heat Shock Protein 70 in Host Defense against T. gondii Infection

“…4, C and D) after injection or non-injection of 1,000 µg of rT.g.HSP70 or vector protein on day 3 PI. T. gondii infection upregulated the production of Th1 cytokines such as IFN-γ and IL-12, peaking at days 4-5 PI, and then subsiding by days 8-10 PI as previously described (9,10,17). Enhancement of Th1 cytokine production was observed at day 1 after rT.g.HSP70 injection (day 4 PI) in T. gondii-infected mice.…”