title: Time series analysis of the transcriptional responses of Biomphalaria glabrata throughout the course of intramolluscan development of Schistosoma mansoni and Echinostoma paraensei.
abstract: Successful colonization of a compatible snail host by a digenetic trematode miracidium initiates a complex, proliferative development program requiring weeks to reach culmination in the form of production of cercariae which, once started, may persist for the remainder of the life span of the infected snail. How are such proliferative and invasive parasites able to circumvent host defenses and establish chronic infections? Using a microarray designed to monitor the internal defense and stress-related responses of the freshwater snail Biomphalaria glabrata, we have undertaken a time course study to monitor snail responses following exposure to two different trematode species to which the snail is susceptible: the medically important Schistosoma mansoni, exemplifying sporocyst production in its larval development, or Echinostoma paraensei, representing an emphasis on rediae production in its larval development. We sampled eight time points (0.5, 1, 2, 4, 8, 16 and 32 days p.i.) that cover the period required for cercariae to be produced. Following exposure to S. mansoni, there was a preponderance of up-regulated over down-regulated array features through 2 days p.i. but by 4 days p.i. and thereafter, this pattern was strongly reversed. For E. paraensei, there was a preponderance of down-regulated array features over up-regulated features at even 0.5 days p.i., a pattern that persists throughout the course of infection except for 1 day p.i., when up-regulated array features slightly outnumbered down-regulated features. Examination of particular array features revealed several that were up-regulated by both parasites early in the course of infection and one, fibrinogen related protein 4 (FREP 4), that remained significantly elevated throughout the course of infection with either parasite, effectively serving as a marker of infection. Many defense-related transcripts were persistently down-regulated, including several fibrinogen-containing lectins and homologs of molecules best known from vertebrate phagocytic cells. Our results are consistent with earlier studies suggesting that both parasites are able to interfere with host defense responses, including a tendency for E. paraensei to do so more rapidly and strongly than S. mansoni. They further suggest mechanisms for how trematodes are able to establish the chronic infections necessary for their continued success.
authors.affiliation: Center for Theoretical and Evolutionary Immunology (CETI), Department of Biology, MSC03 2020, 1 University of New Mexico, Albuquerque, NM 87131, USA. pch1@unm.edu
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Hanington
authors.forename: Cheng-Man
authors.initials: CM
authors.lastname: Lun
authors.forename: Coen M
authors.initials: CM
authors.lastname: Adema
authors.forename: Eric S
authors.initials: ES
authors.lastname: Loker
mesh_terms: D000818:Animals; D001700:Biomphalaria / Q000235:genetics / Q000276:immunology* / Q000469:parasitology*; D015536:Down-Regulation; D004449:Echinostoma / Q000254:growth & development / Q000276:immunology*; D020869:Gene Expression Profiling; D057131:Immune Evasion; D020411:Oligonucleotide Array Sequence Analysis; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D013312:Stress, Physiological; D013997:Time Factors; D015854:Up-Regulation