tetano
Editor, Senior Moderator
PLoS One
. 2026 Aug 12;21(8):e0355607.
doi: 10.1371/journal.pone.0355607. eCollection 2026.
Eosinophil-associated intestinal immune responses following SARS-CoV-2 infection in K18-hACE2 mice
Shun Tamaki[SUP] 1 2 3 [/SUP], Rei Kawashima[SUP] 1 2 3 [/SUP], Takayuki Uematsu[SUP] 4 5 [/SUP], Fumitaka Kawakami[SUP] 2 3 6 [/SUP], Motoki Imai[SUP] 3 7 8 [/SUP], Yoshifumi Kurosaki[SUP] 2 3 9 [/SUP], Toshihide Matsumoto[SUP] 3 10 [/SUP], Shotaro Maehana[SUP] 3 11 12 [/SUP], Yusuke Hara[SUP] 1 13 14 [/SUP], Setsuko Sugawara[SUP] 1 2 3 [/SUP], Hiroki Izawa[SUP] 3 11 12 [/SUP], Takafumi Ichikawa[SUP] 1 2 3 [/SUP], Hidero Kitasato[SUP] 3 11 12 [/SUP], Hideaki Hanaki[SUP] 15 [/SUP], Makoto Kubo[SUP] 3 11 12 [/SUP]
Affiliations
Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is frequently associated with gastrointestinal manifestations; however, intestinal immune responses following SARS-CoV-2 infection remain incompletely understood. This study aimed to characterize eosinophil-associated intestinal immune responses in SARS-CoV-2-infected K18-hACE2 transgenic mice.
Methods: Small intestinal tissues from infected mice were analyzed using cytokine and chemokine PCR arrays, qRT-PCR, immunohistochemistry, and histological analyses.
Results: SARS-CoV-2 infection was associated with marked upregulation of Il5 mRNA in small intestinal tissues, along with increased expression of eosinophil-related cytokines and chemokines, including Ccl24 and Ccl11. Immunohistochemical analyses showed eosinophil accumulation in the lamina propria, accompanied by increased signals for eosinophil-associated granule proteins, including major basic protein and eosinophil peroxidase. Additional qRT-PCR analyses showed increased expression of Prg2 and Epx, further supporting eosinophil granule protein-associated responses. Charcot-Leyden crystals and increased Galectin-10 expression were also observed. Temporal analyses showed an acute Il5/Ccl24-related response followed by delayed Ccl11 upregulation during later stages.
Conclusions: These findings indicate that SARS-CoV-2 infection is associated with eosinophil-associated intestinal immune responses in K18-hACE2 mice. Although eosinophil activation or intestinal allergy was not directly demonstrated, this study supports virus-associated eosinophil-related intestinal responses as a possible framework for understanding allergy-like intestinal immune alterations during SARS-CoV-2 infection.
. 2026 Aug 12;21(8):e0355607.
doi: 10.1371/journal.pone.0355607. eCollection 2026.
Eosinophil-associated intestinal immune responses following SARS-CoV-2 infection in K18-hACE2 mice
Shun Tamaki[SUP] 1 2 3 [/SUP], Rei Kawashima[SUP] 1 2 3 [/SUP], Takayuki Uematsu[SUP] 4 5 [/SUP], Fumitaka Kawakami[SUP] 2 3 6 [/SUP], Motoki Imai[SUP] 3 7 8 [/SUP], Yoshifumi Kurosaki[SUP] 2 3 9 [/SUP], Toshihide Matsumoto[SUP] 3 10 [/SUP], Shotaro Maehana[SUP] 3 11 12 [/SUP], Yusuke Hara[SUP] 1 13 14 [/SUP], Setsuko Sugawara[SUP] 1 2 3 [/SUP], Hiroki Izawa[SUP] 3 11 12 [/SUP], Takafumi Ichikawa[SUP] 1 2 3 [/SUP], Hidero Kitasato[SUP] 3 11 12 [/SUP], Hideaki Hanaki[SUP] 15 [/SUP], Makoto Kubo[SUP] 3 11 12 [/SUP]
Affiliations
- PMID: 42585251
- DOI: 10.1371/journal.pone.0355607
Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is frequently associated with gastrointestinal manifestations; however, intestinal immune responses following SARS-CoV-2 infection remain incompletely understood. This study aimed to characterize eosinophil-associated intestinal immune responses in SARS-CoV-2-infected K18-hACE2 transgenic mice.
Methods: Small intestinal tissues from infected mice were analyzed using cytokine and chemokine PCR arrays, qRT-PCR, immunohistochemistry, and histological analyses.
Results: SARS-CoV-2 infection was associated with marked upregulation of Il5 mRNA in small intestinal tissues, along with increased expression of eosinophil-related cytokines and chemokines, including Ccl24 and Ccl11. Immunohistochemical analyses showed eosinophil accumulation in the lamina propria, accompanied by increased signals for eosinophil-associated granule proteins, including major basic protein and eosinophil peroxidase. Additional qRT-PCR analyses showed increased expression of Prg2 and Epx, further supporting eosinophil granule protein-associated responses. Charcot-Leyden crystals and increased Galectin-10 expression were also observed. Temporal analyses showed an acute Il5/Ccl24-related response followed by delayed Ccl11 upregulation during later stages.
Conclusions: These findings indicate that SARS-CoV-2 infection is associated with eosinophil-associated intestinal immune responses in K18-hACE2 mice. Although eosinophil activation or intestinal allergy was not directly demonstrated, this study supports virus-associated eosinophil-related intestinal responses as a possible framework for understanding allergy-like intestinal immune alterations during SARS-CoV-2 infection.