Eosinophil-associated intestinal immune responses following SARS-CoV-2 infection in K18-hACE2 mice

Abstract

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.