2026-09-22T02:48:33Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/113338 2023-07-11 col_2142_5131 col_2142_14797 com_2142_5130 com_2142_14796 com_2142_397

Steelman, Andrew Das, Aditi Johnson, Rodney Swanson, Kelly Louie, Allison Yukiko 2022-01-12T22:56:13Z 2022-01-12T22:56:13Z 2024-01-12T22:56:20Z 2021-07-21 2021-08 Influenza is one of the most prevalent and devastating infectious diseases in the world. But how host factors may function to increase disease susceptibility or severity has not been fully elucidated. Here, we examined the effects of a high cholesterol diet in modulating the immune response to influenza A virus (IAV) infection in mice. Six-week-old C57BL/6J mice were fed either a standard rodent chow or a matched diet containing 2% cholesterol throughout the experiment. After five weeks of feeding, mice were inoculated with mouse-adapted human IAV (Puerto Rico/8/1934) and tissues were collected at days 0, 4, 8, and 16 post-infection (p.i.). Weights and food disappearance were recorded daily and sickness behavior was evaluated by a burrowing behavior test. Circulating free cholesterol and triglycerides were measured at each time point and diet-induced changes to liver appearance were evaluated at day 16 p.i. Diet-induced changes to T and B cell peripheral responses were assessed, respectively, by measuring MHC Class I-restricted antigen recall responses in the spleen and virus-specific neutralizing antibody levels in the blood. Bulk RNA sequencing was performed on the lungs to evaluate the effect of diet on the lung transcriptome during infection. Diet-induced changes to immune cell populations were determined by flow cytometry. Finally, a crossover design experiment was used to evaluate the effects of diet reversal on IAV-induced morbidity. Cholesterol-fed mice exhibited greater disease morbidity compared to controls fed a normal diet. Dietary cholesterol did not affect the ability to generate an adaptive immune response but rather enhanced it. Cholesterol-fed mice exhibited increased total circulating cholesterol prior to infection and decreased triglycerides after infection as well as altered liver appearance. Gene ontology analysis revealed upregulation of viral-response pathways and leukocyte trafficking to the lungs of mice fed a high cholesterol diet, which coincided with increased number of polyfunctional T cells, CD11bhi DCs, Ly6Chi CD11bhi monocytes and granulocytes, and alveolar macrophages. Taken together, these data indicate that dietary cholesterol may induce a heightened immune response to IAV infection that results in greater morbidity in mature mice. Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2023-08-01 The student, Allison Louie, accepted the attached license on 2021-07-19 at 15:26. The student, Allison Louie, submitted this Thesis for approval on 2021-07-19 at 15:39. This Thesis was approved for publication on 2021-07-21 at 11:27. DSpace SAF Submission Ingestion Package generated from Vireo submission #17015 on 2022-01-12 at 13:05:19 Made available in DSpace on 2022-01-12T22:56:13Z (GMT). No. of bitstreams: 2 LOUIE-THESIS-2021.pdf: 9653110 bytes, checksum: 931bb1a65750a421523cd2eed21e7f98 (MD5) LICENSE.txt: 4210 bytes, checksum: 500b2069dbe8d798d7b427a79c6b817a (MD5) Previous issue date: 2021-07-21 Embargo set by: Seth Robbins for item 121267 Lift date: 2024-01-12T22:56:20Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system Author requested closed access (OA after 2yrs) in Vireo ETD system Limited application/pdf http://hdl.handle.net/2142/113338 en Copyright 2021 Allison Yukiko Louie cholesterol diet influenza infection immune Effects of a high cholesterol diet on the pathogenesis of influenza A virus infection in mature mice text Thesis Nutritional Sciences Nutritional Sciences University of Illinois at Urbana-Champaign Thesis M.S.