Presentation_1_Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats.PDF

Sakai, Yusuke; Mura, Serina; Kuwabara, Yuko; Kagimoto, Saya; Sakurai, Masashi; Morimoto, Masahiro; Park, Eun-sil; Shimojima, Masayuki; Nagata, Noriyo; Ami, Yasushi; Yoshikawa, Tomoki; Iwata-Yoshikawa, Naoko; Fukushi, Shuetsu; Watanabe, Shumpei; Kurosu, Takeshi; Okutani, Akiko; Kimura, Masanobu; Imaoka, Koichi; Saijo, Masayuki; Morikawa, Shigeru; Suzuki, Tadaki; Maeda, Ken

doi:10.3389/fmicb.2023.1333946.s001

Presentation_1_Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats.PDF

presentation

posted on 2024-01-05, 05:08 authored by 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

Introduction

Severe 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.

Methods

Lymph 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.

Results

In 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.

Discussion

These 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.