Abstract
Metalloproteases (MPs) have demonstrated roles in immune modulation. In some cases, these enzymes are produced by parasites to influence host immune responses such that parasite infection is facilitated. One of the best examples of parasite-mediated immune modulation is the matrix metalloprotease (MMP) leishmanolysin (Gp63), which is produced by species of the genus Leishmania to evade killing by host macrophages. Leishmanolysin-like proteins appear to be quite common in many invertebrates, however our understanding of the functions of these non-leishmania enzymes is limited. Numerous proteomic and transcriptomic screens of schistosomes, at all life cycle stages of the parasite, have identified leishmanolysin-like MPs as being present in abundance; with the highest levels being found during the intramolluscan larval stages and being produced by cercaria. This study aims to functionally characterize a Schistosoma mansoni variant of leishmanolysin that most resembles the enzyme produced by Leishmania, termed SmLeish. We demonstrate that SmLeish is an important component of S. mansoni excretory/secretory (ES) products and is produced by the sporocyst during infection. The presence of SmLeish interferes with the migration of Biomphalaria glabrata haemocytes, and causes them to present a phenotype that is less capable of sporocyst encapsulation. Knockdown of SmLeish in S. mansoni miracidia prior to exposure to susceptible B. glabrata reduces miracidia penetration success, causes a delay in reaching patent infection, and lowers cercaria output from infected snails.
Highlights
Compatibility between parasites and their hosts is influenced by a wide variety of immune and immunosuppressive factors that arise over the co-evolutionary history of a host/parasite relationship
Proteomic and transcriptomic screens of schistosomes at all life cycle stages have identified predicted proteins with the hallmark identifiers of metalloproteases, and many are produced in abundance throughout the S. mansoni life cycle [9,10,11,12,13,14,15]; with the highest levels being found during the intramolluscan larval stages and in cercaria [13,14,15]
We demonstrate that SmLeish facilitates the infection of Biomphalaria glabrata snails through interference with B. glabrata haemocyte migration, causing them to be less capable of sporocyst encapsulation
Summary
Compatibility between parasites and their hosts is influenced by a wide variety of immune and immunosuppressive factors that arise over the co-evolutionary history of a host/parasite relationship. Successful trematodes often dampen and/or completely negate specific functions associated with haemocytes, such as the capacity to encapsulate and kill the invading parasite, while conferring a level of protection to other invading trematodes that would typically be targeted and killed [2,3,4]. This process is mediated by the release of products that impact haemocyte mobility, phagocytic activity, attachment, spreading, and production of reactive oxygen species (ROS) [5,6,7]. Proteomic and transcriptomic screens of schistosomes at all life cycle stages have identified predicted proteins with the hallmark identifiers of metalloproteases, and many are produced in abundance throughout the S. mansoni life cycle [9,10,11,12,13,14,15]; with the highest levels being found during the intramolluscan larval stages and in cercaria [13,14,15]
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