Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts

Abstract rag1 −/− zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be...

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Autores principales:	Yumie Tokunaga, Masamichi Shirouzu, Ryota Sugahara, Yasutoshi Yoshiura, Ikunari Kiryu, Mitsuru Ototake, Takahiro Nagasawa, Tomonori Somamoto, Miki Nakao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2e2b8bb39fa4536aa0bf6e4645fb262
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spelling	oai:doaj.org-article:e2e2b8bb39fa4536aa0bf6e4645fb2622021-12-02T15:05:50ZComprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts10.1038/s41598-017-08000-22045-2322https://doaj.org/article/e2e2b8bb39fa4536aa0bf6e4645fb2622017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08000-2https://doaj.org/toc/2045-2322Abstract rag1 −/− zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 −/− zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels. Our developed microscale assays provided evidence that rag1 −/− fish do not possess serum IgM protein, that they do not achieve specific protection even after vaccination, and that they cannot induce antigen-specific CTL activity. The mortality rate in non-vaccinated fish suggests that rag1 −/− fish possess innate protection equivalent to that of rag1 +/− fish. Furthermore, poly(I:C)-induced immune responses revealed that the organ that controls anti-viral immunity is shifted from the spleen to the hepatopancreas due to the absence of T- and B-cell function, implying that immune homeostasis may change to an underside mode in rag-null fish. These findings suggest that the teleost relies heavily on innate immunity. Thus, this model could better highlight innate immunity in animals that lack adaptive immunity than mouse models.Yumie TokunagaMasamichi ShirouzuRyota SugaharaYasutoshi YoshiuraIkunari KiryuMitsuru OtotakeTakahiro NagasawaTomonori SomamotoMiki NakaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yumie Tokunaga Masamichi Shirouzu Ryota Sugahara Yasutoshi Yoshiura Ikunari Kiryu Mitsuru Ototake Takahiro Nagasawa Tomonori Somamoto Miki Nakao Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
description	Abstract rag1 −/− zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 −/− zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels. Our developed microscale assays provided evidence that rag1 −/− fish do not possess serum IgM protein, that they do not achieve specific protection even after vaccination, and that they cannot induce antigen-specific CTL activity. The mortality rate in non-vaccinated fish suggests that rag1 −/− fish possess innate protection equivalent to that of rag1 +/− fish. Furthermore, poly(I:C)-induced immune responses revealed that the organ that controls anti-viral immunity is shifted from the spleen to the hepatopancreas due to the absence of T- and B-cell function, implying that immune homeostasis may change to an underside mode in rag-null fish. These findings suggest that the teleost relies heavily on innate immunity. Thus, this model could better highlight innate immunity in animals that lack adaptive immunity than mouse models.
format	article
author	Yumie Tokunaga Masamichi Shirouzu Ryota Sugahara Yasutoshi Yoshiura Ikunari Kiryu Mitsuru Ototake Takahiro Nagasawa Tomonori Somamoto Miki Nakao
author_facet	Yumie Tokunaga Masamichi Shirouzu Ryota Sugahara Yasutoshi Yoshiura Ikunari Kiryu Mitsuru Ototake Takahiro Nagasawa Tomonori Somamoto Miki Nakao
author_sort	Yumie Tokunaga
title	Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
title_short	Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
title_full	Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
title_fullStr	Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
title_full_unstemmed	Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
title_sort	comprehensive validation of t- and b-cell deficiency in rag1-null zebrafish: implication for the robust innate defense mechanisms of teleosts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e2e2b8bb39fa4536aa0bf6e4645fb262
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Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts

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