Abstract
Background: The unique immunomodulatory capacity of helminth parasites has been investigated as a novel strategy in the prevention of allograft rejection after transplantation. This review was conducted to fully evaluate the specific effects of helminth therapy on allograft survival reported in published studies of animal models of allogeneic transplantation.Method: Following PRISMA protocol guidelines, a literature search was conducted using PubMed, MEDLINE via OvidSP, along with additional manual searches of selected reference lists. Publications describing helminth intervention within allograft transplantation models were screened for relevance to eligibility criteria. Primary and secondary outcomes were extracted using standardized data collection tables. The SYRCLE risk of bias assessment tool was used for quality assessment. Due to heterogeneity of study designs, meta-analysis could not be performed; rather outcomes are presented as a narrative synthesis with concept mapping. This review was registered in PROSPERO with ID: CRD42018097175.Results: The literature search generated 1,443 publications, which after screening for relevance to the eligibility criteria yielded 15 publications for qualitative analysis. All 15 publications reported improvement to allograft survival as a result of helminth therapy. This prolonged allograft survival was not significantly different when helminth-derived products were used compared to live infection. However, the extent of positive impact on allograft survival was noted to be dependent on study design factors, such as the chronicity of the live helminth infection, allograft type and the species/genus of helminth selected.Conclusion: Both live and product-based helminth therapy have potential applications as novel immune regulators or adjuncts for the prevention of allograft rejection. However, there were differences in efficacy between different worms and preparations of worm-derived products. Therefore, further studies are required to determine the most appropriate worm for a specific allograft, to elucidate the optimal dose and route of administration, and to better understand the modulation of immune responses that can mediate tolerance.
Highlights
The unique immunomodulatory capacity of helminth parasites has been investigated as a novel strategy in the prevention of allograft rejection after transplantation
Sample sizes ranged from 5 to 100, with a total of 339 animals infected with live helminth or helminth-derived products across all allograft transplant studies
The positive impacts of helminth therapy on allograft survival were clearly seen across multiple animal models of allogeneic transplantation
Summary
The unique immunomodulatory capacity of helminth parasites has been investigated as a novel strategy in the prevention of allograft rejection after transplantation. Parasitic worms (helminths) are a highly divergent group of macro-pathogens consisting of two major phyla: the Nematoda (or roundworms) and the Platyhelminthes ( known as flatworms), with the latter consisting of both trematodes (flukes) and cestodes (tapeworms) (1) Reflecting this diversity, the course of infection in mammalian hosts varies greatly for different helminths. Infection with Nippostrongylus brasiliensis occurs through subcutaneous infection, unlike the schistosomes that inhabit the mesenteric blood vessels, N. brasiliensis larvae exit the circulation into the lungs and are coughed up and swallowed, eventually residing in the intestine of its chosen mammalian hosts Despite such diversity in the morphology and life cycles of individual helminths, this group of parasites induces a stereotypical Th2 immune response, characterized by the presence of cytokines IL-4, IL-5, IL-13, and IL-10, antibody isotypes IgG1, IgG4, and IgE, and expanded populations of eosinophils, mast cells, basophils and M2 macrophages (2)
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