Efferocytosis-Driven M2 Macrophage Impairs Fibrotic Encapsulation and Promotes Echinococcus multilocularis Growth in Cotton Rats (Sigmodon hispidus)

Manabe, Maru; Nakamura, Teppei; Sato, Keisuke; Hayashi, Naoki; Kouguchi, Hirokazu; Nakao, Ryo; Hidaka, Masahito; Matsuyama, Hiroyuki; Nonaka, Nariaki; Morimatsu, Masami

Efferocytosis-Driven M2 Macrophage Impairs Fibrotic Encapsulation and Promotes Echinococcus multilocularis Growth in Cotton Rats (Sigmodon hispidus)

Manabe, Maru; Nakamura, Teppei; Sato, Keisuke et al.

Microscopy and microanalysis, 2025, 31(5)

Permalink : https://hdl.handle.net/2115/98067

このアイテムのアクセス数:52件（2026-08-25 16:55 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/98067
タイトル	Efferocytosis-Driven M2 Macrophage Impairs Fibrotic Encapsulation and Promotes Echinococcus multilocularis Growth in Cotton Rats (Sigmodon hispidus)
著者	Manabe, Maru ; Nakamura, Teppei ; Sato, Keisuke ; Hayashi, Naoki ; Kouguchi, Hirokazu ; Nakao, Ryo ; Hidaka, Masahito ; Matsuyama, Hiroyuki ; Nonaka, Nariaki ; Morimatsu, Masami
著者名 Manabe, Maru
e-Rad_Researcher 80786773 著者名 Nakamura, Teppei
著者名 Sato, Keisuke
著者名 Hayashi, Naoki
著者名 Kouguchi, Hirokazu
著者名 Nakao, Ryo
著者名 Hidaka, Masahito
著者名 Matsuyama, Hiroyuki
著者名 Nonaka, Nariaki
著者名 Morimatsu, Masami
言語	英語
キーワード	cotton rat
	Echinococcus multilocularis
	efferocytosis
	fibrosis
	macrophage polarization
発行日	2025-10
出版者	Oxford University Press
収録物名	Microscopy and microanalysis
巻(号)	31(5)
抄録	Alveolar echinococcosis, caused by Echinococcus multilocularis, exhibits significant species-dependent susceptibility. This study compared the early hepatic tissue responses to E. multilocularis in highly susceptible cotton rats (Sigmodon hispidus) and laboratory mice (DBA/2 and AKR/N). Following oral administration of E. multilocularis eggs, cotton rats developed a greater number of hepatic lesions within 2 weeks, whereas mice required 4 weeks to develop smaller lesions. Histopathology revealed accelerated multilocular cyst formation in cotton rats. Unlike mice, which formed dense collagenous layers isolating cysts, cotton rats lacked adventitial layers despite similar fibrotic thickness. Immunohistochemistry revealed abundant CD206+ macrophages at cyst peripheries in cotton rats, engaging in efferocytosis of apoptotic neutrophils with expression of TGF-beta, galectin-3, and VEGF. Efferocytic macrophages expressed collagen-degrading enzymes (cathepsin K and MMP9) and the growth factor FGF2. These findings suggest that efferocytosis by neutrophils drives macrophages toward an anti-inflammatory M2 phenotype, leading to immune evasion, ineffective fibrotic encapsulation, and parasitic growth. Given the wide distribution of cotton rats in the Americas and the expanding range of E. multilocularis, their hypersusceptibility raises significant public health concerns as rodents could serve as an intermediate host. These insights may inform new strategies for host-parasite interactions and the control of alveolar echinococcosis.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This is a pre-copyedited, author-produced version of an article accepted for publication in "Microscopy and Microanalysis"following peer review. The version of record Maru Manabe, Teppei Nakamura, Keisuke Sato, Naoki Hayashi, Hirokazu Kouguchi, Ryo Nakao, Masahito Hidaka, Hiroyuki Matsuyama, Nariaki Nonaka, Masami Morimatsu, Efferocytosis-Driven M2 Macrophage Impairs Fibrotic Encapsulation and Promotes Echinococcus multilocularis Growth in Cotton Rats (Sigmodon hispidus), Microscopy and Microanalysis, Volume 31, Issue 5, October 2025, ozaf082, https://doi.org/10.1093/mam/ozaf082 is available online at: https://academic.oup.com/mam/article/31/5/ozaf082/8246674?login=true
PISSN	1431-9276
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1093/mam/ozaf082