非病原性アメーバ(Entamoeba dispar)の腸管感染モデル確立 ー新しい角度からの赤痢アメーバ症における腸管免疫応答の理解に期待ー

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2026-08-07 国立健康危機管理研究機構,東海大学,東京大学

国立健康危機管理研究機構(JIHS)、東海大学、東京大学の共同研究グループは、国内では極めてまれな非病原性アメーバEntamoeba disparの国内初となる臨床分離株(NA442株)の樹立に成功し、この株を用いたマウス腸管感染モデルを確立した。これにより、病原性を持つ赤痢アメーバ(Entamoeba histolytica)との宿主免疫応答を初めて直接比較した。その結果、E. disparは腸管に一定期間定着し、感染初期の免疫応答や軽度の腸粘膜反応は誘導するものの、炎症性サイトカインや好中球浸潤を伴う強い炎症反応は引き起こさず、病原性を示さないことが確認された。また、NA442株は非病原性細菌との単純な共培養で安定維持できることも明らかとなり、病原性アメーバとの代謝や宿主適応の違いを解析する新たな研究基盤が整備された。今後は全ゲノム解析などを通じて病原性を規定する分子機構を解明し、赤痢アメーバ症の発症機序の理解や新たな予防・治療法の開発につながることが期待される。

非病原性アメーバ(Entamoeba dispar)の腸管感染モデル確立 ー新しい角度からの赤痢アメーバ症における腸管免疫応答の理解に期待ー

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日本国内初の臨床分離株を用いたEntamoeba disparに対する腸管免疫応答の評価 Evaluation of intestinal immune responses to Entamoeba dispar using the first domestic clinical isolate in Japan

Yumiko Saito-Nakano,Akira Kawashima,Seiki Kobayashi,Koji Watanabe,Tetsuro Kawano-Sugaya,Shinji Izumiyama,Kumiko Nakada-Tsukui
PLOS Neglected Tropical Diseases  Published: August 6, 2026
DOI:https://doi.org/10.1371/journal.pntd.0014507

Abstract

Background
Entamoeba dispar is a non-pathogenic sibling species of Entamoeba histolytica, yet the mechanisms that enable E. dispar to persist in the intestine without causing disease remain poorly understood. Experimental models for dissecting intestinal immune responses to E. dispar have been limited. In Japan and other East Asian countries, E. histolytica infection is relatively common among men who have sex with men, whereas E. dispar infection has rarely been identified.

Methodology/Principal findings
We report the first domestically acquired and culture-established E. dispar infection in Japan. A clinical strain, NA442, was isolated from fecal cysts of an HIV-positive patient without gastrointestinal symptoms and was maintained in stable monoxenic culture with Pseudomonas putida. Phylogenetic and tRNA-linked STR analyses confirmed the species identity and revealed genetic similarity to a Thailand-derived genotype.

Using NA442, we established a murine cecal infection model to characterize host immune responses. Infection induced detectable secretion of lipocalin-2 in stool, indicating epithelial stress; however, CXCL-1 and myeloperoxidase levels in cecal tissue remained at baseline, and no neutrophil infiltration or tissue destruction was observed. NA442 colonized the murine cecum for up to three weeks but elicited only mild epithelial thickening without the hallmark inflammatory signatures associated with E. histolytica.

Conclusions/Significance
This study provides the first in vivo evidence that E. dispar colonization triggers limited mucosal inflammation despite successful short-term persistence in the intestine. The identification of NA442 as the first domestic E. dispar case in Japan suggests the parasite may circulate unnoticed within the population. The NA442 strain establishes a valuable experimental tool for comparative studies of pathogenic versus non-pathogenic Entamoeba species and contributes to understanding the determinants of intestinal virulence and host immune modulation.

医療・健康
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