A metalloprotease produced by larval Schistosoma mansoni facilitates infection establishment and maintenance in the snail host by interfering with immune cell function

• Published in: PLoS pathogens Vol. 14; no. 10; p. e1007393
• Main Authors: Hambrook, Jacob R, Kaboré, Alèthe L, Pila, Emmanuel A, Hanington, Patrick C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2018; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Biology and Life Sciences; Biomphalaria glabrata; Cell adhesion & migration; Cells, Cultured; Cercaria; Enzymes; Extracellular matrix; Gene expression; Genomes; Glycoproteins; Hemocytes; Host-Parasite Interactions; Immune response; Immune system; Immunomodulation; Infections; Invertebrates; Kinases; Larva - metabolism; Leishmania; Leishmanolysin; Leukocyte migration; Life cycles; Macrophages; Macrophages - immunology; Macrophages - parasitology; Matrix metalloproteinase; Medicine and Health Sciences; Metalloproteases - metabolism; Metalloproteinase; Modulation; Parasites; Parasitology; Peptides; Phenotypes; Proteins; Proteomics; Public health; Schistosoma mansoni; Schistosoma mansoni - enzymology; Schistosomiasis mansoni - parasitology; Screens; Snails; Zinc; Edmonton Alberta Canada; Canada
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007393

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.