한빛사논문
- 조회985
Seongmi K. Russell 1, Jessica K. Harrison 2,3, Benjamin S. Olson 1, Hyung Joo Lee 2,3, Valerie P. O’Brien 1,4, Xiaoyun Xing 2,3, Jonathan Livny 5, Lu Yu 1, Elisha D. O. Roberson 2,6, Rajdeep Bomjan 1, Changxu Fan 2,3, Marina Sha 2,3, Shady Estfanous 7,8, Amal O. Amer 7, Marco Colonna 9, Thaddeus S. Stappenbeck 10, Ting Wang 2,3 , Thomas J. Hannan 1,9 & Scott J. Hultgren 1
1Department of Molecular Microbiology and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St Louis, MO, USA.
2Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.
3Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
4Fred Hutchinson Cancer Center, Human Biology Division, Seattle, WA, USA.
5Infectious Disease and Microbiome Program, The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
6Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St Louis, MO, USA.
7Department of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State University, Columbus, OH, USA.
8Biochemistry and Molecular Biology Department, Faculty of Pharmacy Helwan University, Cairo, Egypt.
9Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
10Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Corresponding authors : Correspondence to Ting Wang, Thomas J. Hannan or Scott J. Hultgren.
Abstract
Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC infection, promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing to sustained cyclooxygenase-2 expression, bladder inflammation and mucosal wounding-responses associated with severe recurrent cystitis. Thus, UPEC infection acts as an epi-mutagen reprogramming the urothelial epigenome, leading to urothelial-intrinsic remodelling and training of the innate response to subsequent infection.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-14)
- 국외 연구진
- 생명과학 > 미생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
