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- W2991287552 abstract "Organoids are multicellular in vitro culture systems that closely resemble the architecture and function of the tissue of origin.Organoids are currently used to study host cell interactions with microorganisms, including viruses, bacteria, and parasites.Helminth research is lacking models that better recapitulate the interaction of the human/livestock host and parasites.Organoid cultures are of great potential to study helminth infections while their application in this field is in its infancy. The different components of the host–helminth in vivo interaction, including tissue architecture, polarization, and multicellularity, environmental cues, and biomechanical forces, should be considered when using organoids to recreate these parasitic infections.In the future, more complex systems integrating stromal and immune cells and microengineering technologies with organoid cultures will further empower the use of this system in helminth research. Organoids are multicellular culture systems that replicate tissue architecture and function, and are increasingly used as models of viral, bacterial, and protozoan infections. Organoids have great potential to improve our current understanding of helminth interactions with their hosts and to replace or reduce the dependence on using animal models. In this review, we discuss the applicability of this technology to helminth infection research, including strategies of co-culture of helminths or their products with organoids and the challenges, advantages, and drawbacks of the use of organoids for these studies. We also explore how complementing organoid systems with other cell types and components may allow more complex models to be generated in the future to further investigate helminth–host interactions. Organoids are multicellular culture systems that replicate tissue architecture and function, and are increasingly used as models of viral, bacterial, and protozoan infections. Organoids have great potential to improve our current understanding of helminth interactions with their hosts and to replace or reduce the dependence on using animal models. In this review, we discuss the applicability of this technology to helminth infection research, including strategies of co-culture of helminths or their products with organoids and the challenges, advantages, and drawbacks of the use of organoids for these studies. We also explore how complementing organoid systems with other cell types and components may allow more complex models to be generated in the future to further investigate helminth–host interactions. Organoids are in vitro multicellular clusters containing various differentiated cell types, capable of self-renewal and organization, and exhibiting some level of functionality and architecture of the tissue of origin [1Fatehullah A. et al.Organoids as an in vitro model of human development and disease.Nat. Cell Biol. 2016; 18: 246-254Crossref PubMed Scopus (915) Google Scholar,2Li M. Izpisua Belmonte J.C. Organoids – preclinical models of human disease.N. Engl. J. Med. 2019; 380: 569-579Crossref PubMed Scopus (169) Google Scholar]. Organoids have transformed biomedical research in the past 10 years. Part of this revolution has been in their use for a better understanding of host–pathogen interactions. Organoid models have been used to investigate viral, bacterial, and protozoan parasite infections [1Fatehullah A. et al.Organoids as an in vitro model of human development and disease.Nat. Cell Biol. 2016; 18: 246-254Crossref PubMed Scopus (915) Google Scholar,3Barrila J. et al.Modeling host–pathogen interactions in the context of the microenvironment: three-dimensional cell culture comes of age.Infect. Immun. 2018; 86 (e00282–18)Crossref PubMed Scopus (88) Google Scholar, 4Dutta D. Clevers H. Organoid culture systems to study host–pathogen interactions.Curr. Opin. Immunol. 2017; 48: 15-22Crossref PubMed Scopus (104) Google Scholar, 5Dutta D. et al.Disease modeling in stem cell-derived 3D organoid systems.Trends Mol. Med. 2017; 23: 393-410Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 6In J.G. et al.Human mini-guts: new insights into intestinal physiology and host–pathogen interactions.Nat. Rev. Gastroenterol. Hepatol. 2016; 13: 633-642Crossref PubMed Scopus (86) Google Scholar]. Helminth infections affect millions of people and livestock, resulting in a major social and economic burden worldwide [7Bethony J. et al.Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm.Lancet. 2006; 367: 1521-1532Abstract Full Text Full Text PDF PubMed Scopus (1637) Google Scholar,8Charlier J. et al.Chasing helminths and their economic impact on farmed ruminants.Trends Parasitol. 2014; 30: 361-367Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar]. Despite their impact, research into helminth infections relies heavily on the use of animals and is limited by a lack of models that more closely reproduce the interaction of the parasites with their specific hosts [9Aebischer T. et al.Editorial: parasite infections: from experimental models to natural systems.Front. Cell Infect. Microbiol. 2018; 8: 12Crossref PubMed Scopus (3) Google Scholar]. In vivo model organisms for human and livestock helminth infection have provided invaluable data on the immune response to helminths, parasite genetics, and transmission. Nevertheless, these models are expensive and complex, hindering the study of host–parasite interactions at the molecular level. Moreover, model organisms cannot fully recapitulate human helminth infections. Entirely new systems are therefore needed that allow the processes of invasion and colonization of human helminths to be studied, and that open up new possibilities for testing new drug targets and identifying vaccine candidates. Organoids from different organs infected by helminths during their life cycle (including gut, lung, bladder, and liver) have enormous potential as novel models for studying the interactions of helminths and their products with their hosts. Nevertheless, the size and complexity of helminths pose challenges on the adaptability of organoid cultures for their use in research. Here, we discuss the applicability of this technology. From our recent investigations into the interactions of whipworm larvae with caecal epithelium and evaluations of the host response to excretory/secretory (ES) products (see Glossary), we explore the advantages and pitfalls of using organoid systems. The implementation of organoid models promises major new avenues for developing new therapeutics and vaccines against helminths, for understanding the anti-inflammatory effects of helminth infections, and for using helminths or their products as alternative therapies to treat inflammatory diseases. Organoids can be derived from either primary tissue stem cells or embryonic or induced pluripotent stem cells (PSCs) when cultured in conditions that resemble those of the stem cell niche (SCN) for a specific organ [1Fatehullah A. et al.Organoids as an in vitro model of human development and disease.Nat. Cell Biol. 2016; 18: 246-254Crossref PubMed Scopus (915) Google Scholar,10Date S. Sato T. Mini-gut organoids: reconstitution of the stem cell niche.Annu. Rev. Cell Dev. Biol. 2015; 31: 269-289Crossref PubMed Scopus (140) Google Scholar,11Clevers H. Modeling development and disease with organoids.Cell. 2016; 165: 1586-1597Abstract Full Text Full Text PDF PubMed Scopus (1614) Google Scholar]. The SCN is a specialized, dynamic and restricted microenvironment where the stem cells reside, and it is composed of physical and cellular components [12Meran L. et al.Intestinal stem cell niche: the extracellular matrix and cellular components.Stem Cells Int. 2017; 2017: 7970385Crossref PubMed Scopus (100) Google Scholar,13Voog J. Jones D.L. Stem cells and the niche: a dynamic duo.Cell Stem Cell. 2010; 6: 103-115Abstract Full Text Full Text PDF PubMed Scopus (290) Google Scholar]. The physical niche comprises the extracellular matrix (ECM), the shape and arrangement of cells and mechanical forces, and the cellular niche refers to the resident immune and stromal cells embedded in the ECM that provide signaling clues to maintain stem cell division and differentiation [12Meran L. et al.Intestinal stem cell niche: the extracellular matrix and cellular components.Stem Cells Int. 2017; 2017: 7970385Crossref PubMed Scopus (100) Google Scholar,14Shoshkes-Carmel M. et al.Subepithelial telocytes are an important source of Wnts that supports intestinal crypts.Nature. 2018; 557: 242-246Crossref PubMed Scopus (303) Google Scholar,15Murrow L.M. et al.Dissecting the stem cell niche with organoid models: an engineering-based approach.Development. 2017; 144: 998-1007Crossref PubMed Scopus (50) Google Scholar]. Current organoid culture conditions combine an ECM support with exogenous growth factors and morphogens (both promoters and inhibitors) that direct the division and differentiation of daughter cells into the multiple cellular populations present in the targeted organ [1Fatehullah A. et al.Organoids as an in vitro model of human development and disease.Nat. Cell Biol. 2016; 18: 246-254Crossref PubMed Scopus (915) Google Scholar,2Li M. Izpisua Belmonte J.C. Organoids – preclinical models of human disease.N. Engl. J. Med. 2019; 380: 569-579Crossref PubMed Scopus (169) Google Scholar,10Date S. Sato T. Mini-gut organoids: reconstitution of the stem cell niche.Annu. Rev. Cell Dev. Biol. 2015; 31: 269-289Crossref PubMed Scopus (140) Google Scholar,11Clevers H. Modeling development and disease with organoids.Cell. 2016; 165: 1586-1597Abstract Full Text Full Text PDF PubMed Scopus (1614) Google Scholar,16Park S.E. et al.Organoids-on-a-chip.Science. 2019; 364: 960-965Crossref PubMed Scopus (389) Google Scholar]. Organoids derived from embryonic or induced PSCs additionally require germ layer- and lineage-specific-factors to direct their differentiation into several endoderm-, mesoderm-, and ectoderm-derived tissues [1Fatehullah A. et al.Organoids as an in vitro model of human development and disease.Nat. Cell Biol. 2016; 18: 246-254Crossref PubMed Scopus (915) Google Scholar,2Li M. Izpisua Belmonte J.C. Organoids – preclinical models of human disease.N. Engl. J. Med. 2019; 380: 569-579Crossref PubMed Scopus (169) Google Scholar,10Date S. Sato T. Mini-gut organoids: reconstitution of the stem cell niche.Annu. Rev. Cell Dev. Biol. 2015; 31: 269-289Crossref PubMed Scopus (140) Google Scholar,11Clevers H. Modeling development and disease with organoids.Cell. 2016; 165: 1586-1597Abstract Full Text Full Text PDF PubMed Scopus (1614) Google Scholar]. Organoid systems were initially developed to recreate murine and human small intestine and colon epithelia, and involved the use of specific culture media cocktails to recreate the SCN conditions for each intestinal segment in the specific species [10Date S. Sato T. Mini-gut organoids: reconstitution of the stem cell niche.Annu. Rev. Cell Dev. Biol. 2015; 31: 269-289Crossref PubMed Scopus (140) Google Scholar,11Clevers H. Modeling development and disease with organoids.Cell. 2016; 165: 1586-1597Abstract Full Text Full Text PDF PubMed Scopus (1614) Google Scholar,17Sato T. Clevers H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications.Science. 2013; 340: 1190-1194Crossref PubMed Scopus (813) Google Scholar]. Subsequently, organoids have been developed for a great variety of tissues and organs, including stomach, esophagus, liver, lung, pancreas, prostate, brain, kidney, mammary gland, ovary, lingual, taste bud, salivary gland, testis, endometrium, Fallopian tube, lymph nodes, blood vessels, skin, inner ear, and retina [1Fatehullah A. et al.Organoids as an in vitro model of human development and disease.Nat. Cell Biol. 2016; 18: 246-254Crossref PubMed Scopus (915) Google Scholar,2Li M. Izpisua Belmonte J.C. Organoids – preclinical models of human disease.N. Engl. J. Med. 2019; 380: 569-579Crossref PubMed Scopus (169) Google Scholar,11Clevers H. Modeling development and disease with organoids.Cell. 2016; 165: 1586-1597Abstract Full Text Full Text PDF PubMed Scopus (1614) Google Scholar,18Kessler M. et al.Chronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation.Nat. Commun. 2019; 10: 1194Crossref PubMed Scopus (55) Google Scholar, 19Wimmer R.A. et al.Human blood vessel organoids as a model of diabetic vasculopathy.Nature. 2019; 565: 505-510Crossref PubMed Scopus (371) Google Scholar, 20Lee J. et al.Hair follicle development in mouse pluripotent stem cell-derived skin organoids.Cell Rep. 2018; 22: 242-254Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 21Lenti E. et al.Therapeutic regeneration of lymphatic and immune cell functions upon lympho-organoid transplantation.Stem Cell Rep. 2019; 12: 1260-1268Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Moreover, intestinal, mammary, keratinocyte, and liver organoids from other animal models already exist, including those of bovine, porcine, ovine, chicken, feline, and canine origin [22Augustyniak J. et al.Organoids are promising tools for species-specific in vitro toxicological studies.J. Appl. Toxicol. 2018; 39: 1610-1622Crossref Scopus (51) Google Scholar]. Currently, organoids are used as models of different pathologies, including infectious diseases caused by viruses, bacteria, and protozoans [3Barrila J. et al.Modeling host–pathogen interactions in the context of the microenvironment: three-dimensional cell culture comes of age.Infect. Immun. 2018; 86 (e00282–18)Crossref PubMed Scopus (88) Google Scholar, 4Dutta D. Clevers H. Organoid culture systems to study host–pathogen interactions.Curr. Opin. Immunol. 2017; 48: 15-22Crossref PubMed Scopus (104) Google Scholar, 5Dutta D. et al.Disease modeling in stem cell-derived 3D organoid systems.Trends Mol. Med. 2017; 23: 393-410Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar]. Viral infection studies with organoid systems have included: norovirus, rotavirus, enteric adenovirus, and coronavirus invasion of intestinal organoids [3Barrila J. et al.Modeling host–pathogen interactions in the context of the microenvironment: three-dimensional cell culture comes of age.Infect. Immun. 2018; 86 (e00282–18)Crossref PubMed Scopus (88) Google Scholar, 4Dutta D. Clevers H. Organoid culture systems to study host–pathogen interactions.Curr. Opin. Immunol. 2017; 48: 15-22Crossref PubMed Scopus (104) Google Scholar, 5Dutta D. et al.Disease modeling in stem cell-derived 3D organoid systems.Trends Mol. Med. 2017; 23: 393-410Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 6In J.G. et al.Human mini-guts: new insights into intestinal physiology and host–pathogen interactions.Nat. Rev. Gastroenterol. Hepatol. 2016; 13: 633-642Crossref PubMed Scopus (86) Google Scholar]; herpes simplex virus 1 [23D'Aiuto L. et al.Modeling herpes simplex virus 1 infections in human central nervous system neuronal cells using two- and three-dimensional cultures derived from induced pluripotent stem cells.J. Virol. 2019; 93 (e00111-19)PubMed Google Scholar] and cytomegalovirus [24Brown R.M. et al.Human cytomegalovirus compromises development of cerebral organoids.J. Virol. 2019; (Published online September 13, 2019)https://doi.org/10.1128/JVI.00957-19Crossref Scopus (40) Google Scholar] infection of cerebral organoids; Zika virus infection of cerebral [4Dutta D. Clevers H. Organoid culture systems to study host–pathogen interactions.Curr. Opin. Immunol. 2017; 48: 15-22Crossref PubMed Scopus (104) Google Scholar,5Dutta D. et al.Disease modeling in stem cell-derived 3D organoid systems.Trends Mol. Med. 2017; 23: 393-410Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar] and human testicular organoids [25Strange D.P. et al.Human testicular organoid system as a novel tool to study Zika virus pathogenesis.Emerg. Microbes Infect. 2018; 7: 82Crossref PubMed Scopus (45) Google Scholar]; human airway organoids to model pathology and assess infectivity of emerging influenza [26Zhou J. et al.Differentiated human airway organoids to assess infectivity of emerging influenza virus.Proc. Natl Acad. Sci. U. S. A. 2018; 115: 6822-6827Crossref PubMed Scopus (162) Google Scholar], parainfluenza [27Porotto M. et al.Authentic modeling of human respiratory virus infection in human pluripotent stem cell-derived lung organoids.mBio. 2019; (Published online May 7, 2019)https://doi.org/10.1128/mBio.00723-19Crossref Scopus (94) Google Scholar] and respiratory syncytial viruses [28Sachs N. et al.Long-term expanding human airway organoids for disease modeling.EMBO J. 2019; 38: e100300Crossref PubMed Scopus (460) Google Scholar]; BK virus infection in human kidney tubuloids [29Schutgens F. et al.Tubuloids derived from human adult kidney and urine for personalized disease modeling.Nat. Biotechnol. 2019; 37: 303-313Crossref PubMed Scopus (239) Google Scholar]; and human liver organoids to study infection with hepatitis B and its related tumorigenesis [30De Crignis E. et al.Human liver organoids; a patient-derived primary model for HBV infection and related hepatocellular carcinoma.bioRxiv. 2019; (Published online March 5, 2019)https://doi.org/10.1101/568147Crossref Google Scholar]. Organoid models of bacterial pathogenesis include enterohaemorrhagic, enteroaggregative, and enteropathogenic Escherichia coli, Vibrio cholerae, Salmonella, Clostridium difficile, and Shigella infecting intestinal organoids of mouse, bovine, porcine, and human origin [3Barrila J. et al.Modeling host–pathogen interactions in the context of the microenvironment: three-dimensional cell culture comes of age.Infect. Immun. 2018; 86 (e00282–18)Crossref PubMed Scopus (88) Google Scholar, 4Dutta D. Clevers H. Organoid culture systems to study host–pathogen interactions.Curr. Opin. Immunol. 2017; 48: 15-22Crossref PubMed Scopus (104) Google Scholar, 5Dutta D. et al.Disease modeling in stem cell-derived 3D organoid systems.Trends Mol. Med. 2017; 23: 393-410Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 6In J.G. et al.Human mini-guts: new insights into intestinal physiology and host–pathogen interactions.Nat. Rev. Gastroenterol. Hepatol. 2016; 13: 633-642Crossref PubMed Scopus (86) Google Scholar,31Derricott H. et al.Developing a 3D intestinal epithelium model for livestock species.Cell Tissue Res. 2019; 375: 409-424Crossref PubMed Scopus (61) Google Scholar], as well as Helicobacter pylori colonizing gastric (stomach) organoids [4Dutta D. Clevers H. Organoid culture systems to study host–pathogen interactions.Curr. Opin. Immunol. 2017; 48: 15-22Crossref PubMed Scopus (104) Google Scholar, 5Dutta D. et al.Disease modeling in stem cell-derived 3D organoid systems.Trends Mol. Med. 2017; 23: 393-410Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 6In J.G. et al.Human mini-guts: new insights into intestinal physiology and host–pathogen interactions.Nat. Rev. Gastroenterol. Hepatol. 2016; 13: 633-642Crossref PubMed Scopus (86) Google Scholar]. In addition, the involvement of bacteria in adenocarcinoma formation in gallbladders has been studied using murine gallbladder organoids infected with Salmonella [4Dutta D. Clevers H. Organoid culture systems to study host–pathogen interactions.Curr. Opin. Immunol. 2017; 48: 15-22Crossref PubMed Scopus (104) Google Scholar,5Dutta D. et al.Disease modeling in stem cell-derived 3D organoid systems.Trends Mol. Med. 2017; 23: 393-410Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar]. Infection with the uropathogen Enterococcus faecalis has been studied in human urothelial organoids [32Horsley H. et al.A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection.Sci. Rep. 2018; 8: 1238Crossref PubMed Scopus (42) Google Scholar]. More recently, Fallopian tube organoids have served as a model to study the long-term impact of Chlamydia trachomatis infections in the human epithelium that may contribute to the development of ovarian cancer [18Kessler M. et al.Chronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation.Nat. Commun. 2019; 10: 1194Crossref PubMed Scopus (55) Google Scholar]. Organoids are also gaining in popularity to model protozoal infections. In particular, Toxoplasma gondii infects bovine and porcine small intestinal organoids [31Derricott H. et al.Developing a 3D intestinal epithelium model for livestock species.Cell Tissue Res. 2019; 375: 409-424Crossref PubMed Scopus (61) Google Scholar]. Furthermore, the entire life cycle of Cryptosporidium parvum can now be modelled in murine and human small intestinal [33Wilke G. et al.A stem-cell-derived platform enables complete cryptosporidium development in vitro and genetic tractability.Cell Host Microbe. 2019; 26: 123-134 e8Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar,34Heo I. et al.Modelling Cryptosporidium infection in human small intestinal and lung organoids.Nat. Microbiol. 2018; 3: 814-823Crossref PubMed Scopus (237) Google Scholar] and lung organoids [34Heo I. et al.Modelling Cryptosporidium infection in human small intestinal and lung organoids.Nat. Microbiol. 2018; 3: 814-823Crossref PubMed Scopus (237) Google Scholar]. Lung organoids have successfully recapitulated respiratory tract infections with C. parvum occurring in immune-competent and -deficient individuals [34Heo I. et al.Modelling Cryptosporidium infection in human small intestinal and lung organoids.Nat. Microbiol. 2018; 3: 814-823Crossref PubMed Scopus (237) Google Scholar]. Research on helminth infections has largely focused on the use of model organisms that have helped us to understand the observations made in patient samples collected in the field (Table 1) [35Inclan-Rico J.M. Siracusa M.C. First responders: innate immunity to helminths.Trends Parasitol. 2018; 34: 861-880Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar]. In recent years, organoids have started to be exploited as a tool to indirectly investigate the effects on the intestinal epithelia of the immune responses triggered by intestinal helminth infections. Specifically, mouse small intestinal organoids have served as an experimental system to demonstrate the expansion of tuft cells as a consequence of ex vivo stimulation with interleukin (IL) 13. IL-13 is secreted by innate lymphoid cells in response to stimulation with IL-25, a cytokine produced by tuft cells during the early response to in vivo infection with the intestinal dwelling nematodes Nippostrongylus brasiliensis, Heligmosomoides polygyrus, and Trichinella spiralis [36Gerbe F. et al.Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites.Nature. 2016; 529: 226-230Crossref PubMed Scopus (572) Google Scholar, 37Howitt M.R. et al.Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut.Science. 2016; 351: 1329-1333Crossref PubMed Scopus (562) Google Scholar, 38von Moltke J. et al.Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit.Nature. 2016; 529: 221-225Crossref PubMed Scopus (756) Google Scholar, 39Luo X.C. et al.Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells.Proc. Natl Acad. Sci. U. S. A. 2019; 116: 5564-5569Crossref PubMed Scopus (115) Google Scholar]. These findings add to the evidence that helminth infections influence stem-cell proliferation and differentiation towards specific epithelial cellular populations, including the goblet cell and the tuft cell compartments that are key for worm expulsion [38von Moltke J. et al.Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit.Nature. 2016; 529: 221-225Crossref PubMed Scopus (756) Google Scholar,40Grencis R.K. Immunity to helminths: resistance, regulation, and susceptibility to gastrointestinal nematodes.Annu. Rev. Immunol. 2015; 33: 201-225Crossref PubMed Scopus (138) Google Scholar]. Comparisons of organoids generated from uninfected and H. polygyrus-infected mice provided further evidence of the impact of helminth infections on stem cell fate within the intestinal crypts. Larval invasion of the submucosal tissue breaches the epithelial barrier, and results in a switch of stem cell phenotype from Lgr5+ to Sca1+, the latter resembling a fetal-like, proliferative, or wound-healing intestinal epithelium profile [41Nusse Y.M. et al.Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche.Nature. 2018; 559: 109-113Crossref PubMed Scopus (151) Google Scholar].Table 1Selection of Human and Livestock Helminth Infections and Life Cycle Stages with Potential to Be Studied Using OrganoidsOrganHelminthHostLife cycle stage relevant to organoid modelsStomach (abomasum)Haemonchus contortus (barber's pole worm)SheepL3 larvae invade epithelium of abomasum and mature to adults that remain attachedSmall intestineAscaris lumbricoides; A. suum (roundworm)Human; pigL3 larvae hatch from ingested eggs, invade epithelium, L4 larvae/adults in lumenToxocara canis, T. cati (roundworm)Human, dog, cat, rodents, rabbit, birdsL2 larvae hatch from ingested eggs, invade epithelium, L3/L4/ L5 and adults in lumenHeligmosomoides polygyrusMouseIngested L3 larvae invade epithelium and submucosa; re-emerge as adults into lumenTrichinella spiralis (pork worm)Human, pig, mouseL1 larvae invade epithelium and mature to adultsNecator americanus, Ancylostoma duodenale (hookworms); Nippostrongylus brasiliensisHuman; mouse, ratL4 larvae/adult worms in lumen (L3 enter through skin)Strongyloides stercoralis (thread worm); S. venezuelensis, S. rattiHuman, dog; mouse, ratL4 larvae/adult worms in lumen (L3 enter through skin)Taenia saginata, T. solium (tapeworms); T. taeniaeformis, T. crassicepsHuman, pig, ruminants; mouse, ratIngested larvae (cysticerci) attach to epithelium, grow to adultsEchinococcus granulosus, E. multilocularis (tapeworms)Human, dog, cat, cattle, horse, sheep, pig, rodentsEggs ingested by the first host hatch releasing oncospheres (larvae) that penetrate the epithelium and submucosa.Cysts and protoscolices that are ingested by a second host attach to epithelium and develop into adultsFasciola hepatica, F. gigantica (liver fluke)Human, sheep, cattle, mouseNewly excisted juvenile (larvae) penetrate the intestinal wall of the duodenum into peritoneal cavitySmall and large intestineSchistosoma mansoni, S. japonicum (blood fluke)Human, mouseAdults in mesenteric veins produce eggs which transit intestinal wall to lumenLarge intestineTrichuris trichiura; T. muris; T. suis (whipworm)Human; mouse; pigL1 larvae invade caecal/large intestinal epithelium and mature to adultsSkinN. americanus, A. duodenale;N. brasiliensisHuman; mouse, ratFree-living L3 larvae penetrate unbroken skinS. stercoralis; S. venezuelensis, S. rattiHuman, dog; mouse, ratFree-living L3 larvae penetrate unbroken skinS. mansoni, S. haematobium,S. japonicumHuman, mouseFree-swimming cercariae in freshwater penetrate unbroken skinLungT. canis, T. catiHuman, dog, cat, cattle, horse, sheep, pig, rodentsL2/L3 larvae transit lung where may encapsulate or migrate through trachea and oesophagus to gutN. americanus, A. duodenale;N. brasiliensis; Ascaris sppHuman; mouse, rat; pigDeveloping L3/L4 stages transit lung, migrate through trachea and oesophagus to gutS. stercoralis; S. venezuelensis, S. rattiHuman, dog; mouse, ratL3 larvae transit lung, migrate through trachea and oesophagus to gutS. mansoni, S. haematobium,S. japonicumHuman, mouseSchistosomulae (larvae) develop prior to migration to vascular nicheE. granulosusHuman, dog, cat, cattle, horse, sheep, pig, rodentsOncospheres (larvae) circulate to the lungs where they develop into cysts and protoscoliscesLiverT. canis, T. catiHuman, dog, cat, cattle, horse, sheep, pig, rodentsL2 larvae transit liver where may encapsulate or migrate to the lungS. mansoni, S. japonicumHuman, mouseEggs frequently trapped in liver, pathogenicE. granulosus, E. multilocularisHuman, dog, cat, cattle, horse, sheep, pig, rodentsOncospheres (larvae) circulate to the liver where they develop into cysts and protoscoliscesF. hepatica, F. giganticaHuman, sheep, cattle, mouseMigrating juvenile and adultsBrainT. solium, Mesocestoides cortiHuman, mouseCysts form in brainBladderS. haematobiumHuman, mouseEggs from adults breach barrier to reach urinary tractLymphatics/blood vesselsBrugia malayi (and other lymphatic filariae)HumanAdults live in lymphatic system, microfilariae in peripheral blood Open table in a new tab Organoids have also been utilized in experiments that aim to characterize the interactions and intestinal epithelial responses to ES products of various nematodes. In particular, stimulation of murine small intestine organoids with ES products and extracts of T. spiralis showed that sensing of parasitic products by tuft cell receptors results in Ca2+ responses [39Luo X.C. et al.Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells.Proc. Natl Acad. Sci. U. S. A. 2019; 116: 5564-5569Crossref PubMed Scopus (115) Google Scholar]. Moreover, imaging experiments of murine small intestine and colon organoids, microinjected with exosome-like extracellular vesicles (EVs) present in the ES of N. brasiliensis and Trichuris muris, respectively, showed their internalization by host epithelial cells [42Eichenberger R.M. et al.Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication.J. Extracell. Vesicles. 2018; 7: 1428004Crossref PubMed Scopus (88) Google Scholar,43Eichenberger R.M. e" @default.
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- W2991287552 title "Organoids – New Models for Host–Helminth Interactions" @default.
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