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.
Highlights
Schistosome parasites have six different morphological stages during their life cycle, which requires an intermediate molluscan and a definitive mammalian host that the parasite must correctly identify and invade
We describe a role for heat shock protein 70 (Hsp70) in cercarial invasion behavior
Only generic stimulation with skin lipid, linoleic acid or L-arginine are known to induce cercarial invasion behavior; we can begin an initial investigation of molecular requirements for host invasion and environment transition for schistosomes and possibly other parasitic organisms
Summary
Schistosome parasites have six different morphological stages during their life cycle, which requires an intermediate molluscan and a definitive mammalian host that the parasite must correctly identify and invade. Free-swimming, freshwater cercariae (singular: cercaria) are released from infected molluscs and invade mammals and humans for further development into larval worms called schistosomula (singular: schistosomulum or schistosomule). Cercariae are highly adapted for swimming and invading their mammalian hosts. Free-swimming cercariae have a limited energy supply and a limited duration during which they can infect their host [4]. They must correctly identify and quickly respond to an appropriate host (or source of chemoattractant), swim toward it, and begin the host penetration process. Parasite invasion through the skin involves the physical motion of swimming into the skin, in coordination with release of their acetabular gland contents, which include mucins to enhance the attachment to skin and proteases to degrade skin molecules [10,11,12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
