The Schistosoma mansoni Tegumental-Allergen-Like (TAL) Protein Family: Influence of Developmental Expression on Human IgE Responses

Abstract

Background A human IgE response to Sm22.6 (a dominant IgE target in Schistosoma mansoni ) is associated with the development of partial immunity. Located inside the tegument, the molecule belongs to a family of proteins from parasitic platyhelminths, the Tegument-Allergen-Like proteins (TALs). In addition to containing dynein-light-chain domains, these TALs also contain EF-hand domains similar to those found in numerous EF-hand allergens. Methodology/Principal Findings S. mansoni genome searches revealed 13 members (SmTAL1-13) within the species. Recent microarray data demonstrated they have a wide range of life-cycle transcriptional profiles. We expressed SmTAL1 (Sm22.6), SmTAL2, 3, 4, 5 and 13 as recombinant proteins and measured IgE and IgG4 in 200 infected males (7–60 years) from a schistosomiasis endemic region in Uganda. For SmTAL1 and 3 (transcribed in schistosomula through adult-worms and adult-worms, respectively) and SmTAL5 (transcribed in cercariae through adult-worms), detectable IgE responses were rare in 7–9 year olds, but increased with age. At all ages, IgE to SmTAL2 (expressed constitutively), was rare while anti-SmTAL2 IgG4 was common. Levels of IgE and IgG4 to SmTAL4 and 13 (transcribed predominantly in the cercariae/skin stage) were all low. Conclusions We have not measured SmTAL protein abundance or exposure in live parasites, but the antibody data suggests to us that, in endemic areas, there is priming and boosting of IgE to adult-worm SmTALs by occasional death of long-lived worms, desensitization to egg SmTALs through continuous exposure to dying eggs and low immunogenicity of larval SmTALs due to immunosuppression in the skin by the parasite. Of these, it is the gradual increase in IgE to the worm antigens that parallels age-dependent immunity seen in endemic areas.

FhCaBP1 (FH22): A Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains

“…Similar proteins are found in other species from the phylum Platyhelminthes . The best characterised of these are the tegumental allergen like (TAL) proteins from Schistosoma mansoni (Fitzsimmons, et al, 2012, Francis and Bickle, 1992, Hoffmann and Strand, 1997, Jeffs, et al, 1991, Mohamed, et al, 1998, Santiago, et al, 1998. This species expresses 13 family members, some of which have been shown to elicit IgE-mediated immune responses in the host (Fitzsimmons, et al, 2012, Fitzsimmons, et al, 2007, Webster, et al, 1997.…”

“…The best characterised of these are the tegumental allergen like (TAL) proteins from Schistosoma mansoni (Fitzsimmons, et al, 2012, Francis and Bickle, 1992, Hoffmann and Strand, 1997, Jeffs, et al, 1991, Mohamed, et al, 1998, Santiago, et al, 1998. This species expresses 13 family members, some of which have been shown to elicit IgE-mediated immune responses in the host (Fitzsimmons, et al, 2012, Fitzsimmons, et al, 2007, Webster, et al, 1997. Proteins from this family have also been identified and characterised from other species in the genus Schistosoma, from the Chinese liver fluke Clonorchis sinensis (Huang, et al, 2007, Kim, et al, 2012, Senawong, et al, 2012, Subpipattana, et al, 2012, Vichasri-Grams, et al, 2006, the giant liver fluke Fasciola gigantica and the carcinogenic liver fluke, Opisthorchis viverrini (Fitzsimmons, et al, 2004, Li, et al, 2000, Santiago, et al, 1998, Waine, et al, 1994, Xu, et al, 2014, Zhang, et al, 2012.…”

“…While many of the proteins have been localised to the tegument of the worm, their in vivo functions have not been elucidated (Fitzsimmons, et al, 2012, Havercroft, et al, 1990, Huang, et al, 2007, Kim, et al, 2012, Lopes, et al, 2009, Mohamed, et al, 1998, Subpipattana, et al, 2012, Xu, et al, 2014, Zhang, et al, 2012. From the available data it is evident that, despite clear sequence similarities, differences exist between the proteins at the biochemical level.…”

Effects of Treatment on IgE Responses against Parasite Allergen-Like Proteins and Immunity to Reinfection in Childhood Schistosome and Hookworm Coinfections

“…In schistosomiasis, IgE to adult worm antigens has been associated with resistance to reinfection (5)(6)(7)(8); these responses tend to increase with age and after chemotherapeutic treatment in populations in which the disease is endemic (9,10). In hookworm infection, negative relationships between both total and specific IgE and worm weight, fecundity, and heavy hookworm infection have been described (11,12).…”

“…For example, IgE to Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1-IgE) is a marker for human immunity in schistosomiasis mansoni (5,16); SmTAL1 is a member of the TAL family, a group of proteins sharing structural homology with the EF hand allergens, one of the most common groups of clinical allergens (9). In necatoriasis americanus, negative associations between IgE to the recombinant larval protein Necator americanus Ancylostoma-secreted protein-2 (Na-ASP-2) and heavy infection intensity have been described (11); Na-ASP-2 shares structural homology with the pathogenesis-related 1 (PR-1) allergens, the majority of which are derived from insect venoms (18).…”