Schistosoma mansoni excretory secretory products induce protein kinase signalling, hyperkinesis, and stem cell proliferation in the opposite sex

Abstract

Adult male and female schistosomes in copula dwell within human blood vessels and lay eggs that cause the major Neglected Tropical Disease human schistosomiasis. How males and females communicate to each other is poorly understood; however, male-female physical interaction is known to be important. Here, we investigated whether excretory-secretory products (ESPs), released into the external milieu by mature Schistosoma mansoni, might induce responses in the opposite sex. We demonstrate that ESPs adhere to the surface of opposite sex worms inducing the activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways, particularly in the parasite tegument. Furthermore, we show that mature worms stimulated signalling in juvenile worms. Strikingly, we demonstrate that ESPs from the opposite sex promote stem cell proliferation, in an ERK- and p38 MAPK-dependent manner, in the tegument and within the testes of males, and the ovaries and vitellaria of females. Hyperkinesia also occurred following opposite sex ESP exposure. Our findings support the novel concept that male and female schistosomes may communicate over distance to modulate key processes underlying worm development and disease progression, opening novel avenues for schistosomiasis control.

Human growth factor-mediated signalling through lipid rafts regulates stem cell proliferation, development and survival of Schistosoma mansoni

“…To investigate the effect of cholesterol depletion and EGFR inhibition on stem cell proliferation in somules, Click-iT EdU with Alexa Fluor 594 azide (Thermo Fisher Scientific) was used according to described protocols [101,102] and manufacturer's instructions. All stages of somules were washed briefly in warmed BME and were transferred to individual wells of a 96-well tissue culture plate (Nunc) with 100 µl warmed BME supplemented with antibiotics/antimycotics.…”