Browsing by Author "Yoon, Grace Haewon"

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    Neutrophil localization during C. rodentium-induced colitis
    (2024-05-06) Yoon, Grace Haewon; Cobo, Eduardo; McKay, Derek; Mody, Christopher
    Intestinal infections by enteropathogenic bacteria like Escherichia coli pose a significant risk to human health worldwide and can contribute to a wide spectrum of different symptoms and diseases. The infection can result in weight loss, diarrhea, hemorrhagic colitis, dehydration and potentially death. To study enteropathogenic colonization further, a murine Citrobacter rodentium (C. rodentium) model is used in this project to understand the activity of neutrophils, often the first cell line of defense, during infection. While it is known that neutrophils are involved in the eradication of C. rodentium, their presence during different phases of C. rodentium infection and functions at these time points, such as inflammation regulation and clearance, remain unknown, especially in the context of recruitment, location, and time. During an infection within the intestine, pathogens encounter many different obstacles such as the mucus layer, intestinal epithelial cells, and innate immune cells. Neutrophils are innate immune cells that are well recognized as first responders during infections, and they are armed with granules that contain toxic agents such as reactive oxygen species, proteases, and antimicrobial peptides/proteins. In the context of C. rodentium infection, it has been shown that neutrophils preferentially phagocytose the bacteria within the cecal lumen during the steady phase of infection; however, the localization and distribution of neutrophils throughout the progression of the infection remains elusive. Previous studies have alluded to the potential of localization in determining function of neutrophils where neutrophils that have undergone transepithelial migration have more bactericidal capabilities. As such, exploring the localization and distribution throughout the different phases of C. rodentium can shed light on the roles that neutrophils play during the infection. Our findings show that neutrophils are abundantly recruited within the colonic mucosa during the acute inflammation phase (7 dpi) and reach the colonic lumen. Cathelicidin, an antimicrobial peptide, deficiency leads to more neutrophil recruitment than its wildtype counterpart upon infection. Furthermore, the bulk RNA sequencing results show that NET formation and degranulation are upregulated neutrophil functions during C. rodentium infection in both cathelicidin-deficient and wildtype mice. By further understanding the behaviour and activity of neutrophils during infection, it can allow us to harness the microbicidal ability of these cells to use as a potential therapeutic in years to come.