Hsp70 May Be a Molecular Regulator of Schistosome Host Invasion

Abstract

Schistosomiasis is a debilitating disease that affects over 240 million people worldwide and is considered the most important neglected tropical disease following malaria. Free-swimming freshwater cercariae, one of the six morphologically distinct schistosome life stages, infect humans by directly penetrating through the skin. Cercariae identify and seek the host by sensing chemicals released from human skin. When they reach the host, they burrow into the skin with the help of proteases and other contents released from their acetabular glands and transform into schistosomula, the subsequent larval worm stage upon skin infection. Relative to host invasion, studies have primarily focused on the nature of the acetabular gland secretions, immune response of the host upon exposure to cercariae, and cercaria-schistosomulum transformation methods. However, the molecular signaling pathways involved from host-seeking through the decision to penetrate skin are not well understood. We recently observed that heat shock factor 1 (Hsf1) is localized to the acetabular glands of infectious schistosome cercariae, prompting us to investigate a potential role for heat shock proteins (HSPs) in cercarial invasion. In this study, we report that cercarial invasion behavior, similar to the behavior of cercariae exposed to human skin lipid, is regulated through an Hsp70-dependent process, which we show by using chemical agents that target Hsp70. The observation that biologically active protein activity modulators can elicit a direct and clear behavioral change in parasitic schistosome larvae is itself interesting and has not been previously observed. This finding suggests a novel role for Hsp70 to act as a switch in the cercaria-schistosomulum transformation, and it allows us to begin elucidating the pathways associated with cercarial host invasion. In addition, because the Hsp70 protein and its structure/function is highly conserved, the model that Hsp70 acts as a behavior transitional switch could be relevant to other parasites that also undergo an invasion process and can apply more broadly to other organisms during morphological transitions. Finally, it points to a new function for HSPs in parasite/host interactions.

The in vivo transcriptome of Schistosoma mansoni in the prominent vector species Biomphalaria pfeifferi with supporting observations from Biomphalaria glabrata

“…sHSP 40 has been identified as a soluble egg antigen responsible for eliciting immunopathological reactions in the definitive host that result in granuloma formations [119]. Ishida and Jolly [120] showed that in the absence of HSP 70, cercariae do not orient or penetrate normally, providing additional functional roles for HSP 70 beyond stress responses. We noted that S .…”

A Tail of Two Structures: Proteomic and Transcriptomic Analysis of Cercarial Heads and Tails of Schistosome Worms

“…The complex of HSP70-HSP40 can also interact with the ribosomal-associated complex and assist translation and link protein folding to translation directly. We have shown a role for HSP70 in signaling homing behavior in cercariae, but the role of HSP40 is less clear [53]. Two potential roles for HSP40 repression would be the reduction of the HSP70-HSP40 complexing to allow HSP70 to perform its role in host detection and homing or HSP70 ATPase activity needs to remain inhibited to maintain its pre-homing state.…”

Phosphoproteomics analysis of male and female Schistosoma mekongi adult worms

“…Heat shock proteins (Hsp)60, 70, 71, and 90 are present on spermatocytes 39 , 40 . Importantly, Hsp70 of schistosome contributes to cercaria-schistosomulum transformation and is associated with cercarial host invasion 41 . Because heat shock protein is involved in the early stage after infection, it is a fascinating target by which to block invasion by schistosomes.…”