Effects of Estradiol and Progesterone-Induced Intracellular Calcium Fluxes on Toxoplasma gondii Gliding, Microneme Secretion, and Egress.

Qun Liu,Jing Liu,Yong Fu,Heng Zhang,Xiao Zhang

doi:10.3389/fmicb.2018.01266

Abstract

Research has shown that estrogen is present and plays a critical role in vertebrate reproduction and metabolism, but the influence of steroids on Toxoplasma gondii has received less attention. Our data showed that estradiol and progesterone induced parasitic cytosolic Ca2+ fluxes. This process required estrogen to enter the cytoplasm of T. gondii, and cGMP-dependent protein kinase G (PKG) and phosphoinositide-phospholipase C (PI-PLC) emerged as important factors controlling parasitic intracellular (IC) Ca2+ signals. Cytosolic Ca2+, which is regulated by estradiol, was mostly mobilized from acidic organelles. Moreover, cytosolic Ca2+ slightly increased MIC2 protein secretion and promoted the gliding motility and egress of parasites, thus enhancing the pathogenicity of T. gondii, as shown in our previous research. We subsequently determined that the main source of Ca2+ regulated by progesterone was a neutral store. In contrast to the findings of estradiol, progesterone reduced MIC2 protein secretion and inhibited the gliding motility of parasites, which may decrease their pathogenicity. Additionally, unlike in mammals, estradiol and progesterone had no effect on nitric oxide (NO) or reactive oxygen species (ROS) production in T. gondii.

Highlights

Toxoplasma gondii is found worldwide, and this pathogen can infect a wide range of hosts, such as humans, livestock, pets, and wildlife
Estrogen is associated with T. gondii invasion and proliferation, which has been discussed in our previous work, and Ca2+ signaling is crucial in parasite biology
We extend our understanding of the effects of estrogen on T. gondii by demonstrating that protein kinase G (PKG) and phosphoinositidephospholipase C (PI-PLC) activities are important for the robust Ca2+ response elicited by estrogen

Summary

Introduction

Toxoplasma gondii is found worldwide, and this pathogen can infect a wide range of hosts, such as humans, livestock, pets, and wildlife. All karyocytes are considered to be definitive cells of T. gondii (Montoya and Liesenfeld, 2004). T. gondii has been held responsible for high morbidity in some special cases, such as the high transmission frequency of T. gondii observed during pregnancy (Roberts et al, 2001). Concentrations of estradiol and progesterone are several-fold higher in pregnant females than in non-pregnant females, and the infection rate of pathogens is significantly increased. The fact that pathogens can utilize sex steroid hormones for their survival and reproductive success is often overlooked (Vom Steeg and Klein, 2016).

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