Tachyzoite to bradyzoite conversion Bradyzoite to tachyzoite conversion
High pHa Lack of NO
Low pHa Lack of IFN-γ
Heat shockb Lack of TNF-α
Mitochondrial inhibitionc Lack of IL-12
Presence of NOc Lack of T cells
Elevation of both cAMP and cGMPd Induction of a variety of HSPs,including HSP70, is associated with bradyzoite transitione
aOne cannot exclude that the differences in therapeutic efficacy between valproic acid and sodium valproate used in several neuropsychiatric diseases were related to acidic or alkaline target local tissue conditions induced by these two pharmaceutical forms of a drug (low doses vs. high doses, respectively) [577,578]. bPhysiologically relevant circumstances that could play a role in stage conversion in vivo include heat shock through a fever [576]. cNO overproduction in ASD individuals [579] is an inhibitor of mitochondrial function [106]. dStress-induced elevation of cAMP could play a role in bradyzoite induction because addition of cAMP or cGMP to tachyzoites can stimulate stage conversion [580]. PLK, a T. gondii ME49 clonal strain able to differentiate in vitro, exhibited a rise in cAMP in response to bradyzoite inducing conditions, but elevation of cAMP under the same conditions was not evident in RH, a strain that does not differentiate well [580]. It must be emphasized that inducers of oxidative stress (nb. a state characteristic for autistic patients) also have been demonstrated to cause parasite encystment in vitro [581,582]
Table 36: Factors associated with tachyzoite and bradyzoite interconversion (according to Lyons et al. [576]; with own modification).