Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats
IntroductionSevere fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1333946/full |
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| author | Yusuke Sakai Serina Mura Yuko Kuwabara Saya Kagimoto Masashi Sakurai Masahiro Morimoto Eun-sil Park Masayuki Shimojima Noriyo Nagata Yasushi Ami Tomoki Yoshikawa Naoko Iwata-Yoshikawa Shuetsu Fukushi Shumpei Watanabe Takeshi Kurosu Akiko Okutani Masanobu Kimura Koichi Imaoka Masayuki Saijo Shigeru Morikawa Tadaki Suzuki Ken Maeda |
| author_facet | Yusuke Sakai Serina Mura Yuko Kuwabara Saya Kagimoto Masashi Sakurai Masahiro Morimoto Eun-sil Park Masayuki Shimojima Noriyo Nagata Yasushi Ami Tomoki Yoshikawa Naoko Iwata-Yoshikawa Shuetsu Fukushi Shumpei Watanabe Takeshi Kurosu Akiko Okutani Masanobu Kimura Koichi Imaoka Masayuki Saijo Shigeru Morikawa Tadaki Suzuki Ken Maeda |
| author_sort | Yusuke Sakai |
| collection | DOAJ |
| description | IntroductionSevere fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited. Thus, in this study, we characterized the germinal centre response and apoptosis in the lymph nodes of cats with fatal SFTS, because SFTS in cats well mimics the pathology of human SFTS.MethodsLymph node tissue sections collected during necropsy from seven fatal SFTS patients and five non-SFTS cases were used for histopathological analysis. Additionally, lymph node tissue sections collected from cats with experimental infection of SFTS virus (SFTSV) were also analysed.ResultsIn the lymphoid follicles of cats with SFTS, a drastic decrease in Bcl6- and Ki67-positive germinal centre B cells was observed. Together, the number of T cells in the follicles was also decreased in SFTS cases. In the paracortex, a marked increase in cleaved-caspase3 positivity was observed in T cells. These changes were independent of the number of local SFTS virus-positive cell. Furthermore, the analysis of cats with experimental SFTSV infection revealed that the intrafollicular Bcl6- and CD3-positive cell numbers in cats with low anti-SFTSV antibody production were significantly lower than those in cats with high anti-SFTSV antibody production.DiscussionThese results suggest that dysfunction of the humoral response in severe SFTS was caused by the loss of germinal centre formation and massive apoptosis of T cells in the lymph nodes due to systemically circulating viruses. |
| first_indexed | 2024-03-08T16:49:46Z |
| format | Article |
| id | doaj.art-19c571c299524b6ba213c21b4b30f967 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-08T16:49:46Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-19c571c299524b6ba213c21b4b30f9672024-01-05T05:17:47ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-01-011410.3389/fmicb.2023.13339461333946Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in catsYusuke Sakai0Serina Mura1Yuko Kuwabara2Saya Kagimoto3Masashi Sakurai4Masahiro Morimoto5Eun-sil Park6Masayuki Shimojima7Noriyo Nagata8Yasushi Ami9Tomoki Yoshikawa10Naoko Iwata-Yoshikawa11Shuetsu Fukushi12Shumpei Watanabe13Takeshi Kurosu14Akiko Okutani15Masanobu Kimura16Koichi Imaoka17Masayuki Saijo18Shigeru Morikawa19Tadaki Suzuki20Ken Maeda21Department of Pathology, National Institute of Infectious Diseases, Tokyo, JapanLaboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, JapanLaboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, JapanLaboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, JapanLaboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, JapanLaboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, JapanDepartment of Veterinary Science, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Pathology, National Institute of Infectious Diseases, Tokyo, JapanManagement Department of Biosafety and Laboratory Animal, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Pathology, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, JapanFaculty of Veterinary Medicine, Okayama University of Science, Ehime, JapanDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Veterinary Science, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Veterinary Science, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Veterinary Science, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, JapanFaculty of Veterinary Medicine, Okayama University of Science, Ehime, JapanDepartment of Pathology, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Veterinary Science, National Institute of Infectious Diseases, Tokyo, JapanIntroductionSevere fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited. Thus, in this study, we characterized the germinal centre response and apoptosis in the lymph nodes of cats with fatal SFTS, because SFTS in cats well mimics the pathology of human SFTS.MethodsLymph node tissue sections collected during necropsy from seven fatal SFTS patients and five non-SFTS cases were used for histopathological analysis. Additionally, lymph node tissue sections collected from cats with experimental infection of SFTS virus (SFTSV) were also analysed.ResultsIn the lymphoid follicles of cats with SFTS, a drastic decrease in Bcl6- and Ki67-positive germinal centre B cells was observed. Together, the number of T cells in the follicles was also decreased in SFTS cases. In the paracortex, a marked increase in cleaved-caspase3 positivity was observed in T cells. These changes were independent of the number of local SFTS virus-positive cell. Furthermore, the analysis of cats with experimental SFTSV infection revealed that the intrafollicular Bcl6- and CD3-positive cell numbers in cats with low anti-SFTSV antibody production were significantly lower than those in cats with high anti-SFTSV antibody production.DiscussionThese results suggest that dysfunction of the humoral response in severe SFTS was caused by the loss of germinal centre formation and massive apoptosis of T cells in the lymph nodes due to systemically circulating viruses.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1333946/fullsevere fever with thrombocytopenia syndromecatshistopathologylymph nodesgerminal centre reaction |
| spellingShingle | Yusuke Sakai Serina Mura Yuko Kuwabara Saya Kagimoto Masashi Sakurai Masahiro Morimoto Eun-sil Park Masayuki Shimojima Noriyo Nagata Yasushi Ami Tomoki Yoshikawa Naoko Iwata-Yoshikawa Shuetsu Fukushi Shumpei Watanabe Takeshi Kurosu Akiko Okutani Masanobu Kimura Koichi Imaoka Masayuki Saijo Shigeru Morikawa Tadaki Suzuki Ken Maeda Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats Frontiers in Microbiology severe fever with thrombocytopenia syndrome cats histopathology lymph nodes germinal centre reaction |
| title | Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats |
| title_full | Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats |
| title_fullStr | Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats |
| title_full_unstemmed | Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats |
| title_short | Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats |
| title_sort | lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive t cell apoptosis in cats |
| topic | severe fever with thrombocytopenia syndrome cats histopathology lymph nodes germinal centre reaction |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1333946/full |
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