Exploring the Insights of Intestinal Epithelial Cell-intrinsic Anti-Cryptosporidium Defense

Monday, October 7, 2024 at 12 PM EST

Xian Ming-Chen, PhD
Professor, Microbial Pathogens and Immunity, Rush University

Hybrid seminar in Hill 132 and via Zoom: https://upenn.zoom.us/j/91485597704

 

ABSTRACT:

Given its intra-cellular but extra-cytoplasmic localization after Cryptosporidium (Crypto) host cell entry, epithelial cell-intrinsic defense plays a critical role in host anti-Crypto defense, of which, IFNs play a critical role. Intestinal epithelial cells (IECs) are equipped with the necessary molecular machinery to mount cell-intrinsic defensive responses. Activation of pattern recognition receptors in IECs following Crypto infection leads to the upregulation of antimicrobial factors, secretion of cytokines and chemokines (such as IFNs), and conditioning of immune cells for direct antimicrobial action or instruction of adaptive immune responses. LncRNAs are long non-coding transcripts that can regulate gene expression through their interactions with other effect molecules. A panel of lncRNAs are upregulated in IECs following Crypto infection. Whereas host cells can promote cell-intrinsic antimicrobial defense via induction of defensive lncRNAs, Crypto may also hijack distinct host lncRNAs to interfere with IFN-γ-mediated antimicrobial defense, beneficial to parasite survival. The N6-methyladenosine (m6A) RNA methylation is one of the most prevalent reversible RNA post-transcriptional modifications in mammalian cells. IFN-γ-responsive lncRNAs (e.g., Nostrill) can modulate the m6A methylation levels of several IFN-γ-stimulated immune gene transcripts, contributing to the regulation of epithelial cell-intrinsic anti-Crypto defense. Moreover, C. parvum infection impairs bile acid reabsorption in the ileum and disturbs lipid metabolism and bile acid homeostasis across the enterohepatic circulation. Bile gavage can significantly reduce the infection burden and ameliorates the dysregulated homeostasis of cell proliferation and migration in intestinal epithelium following infection.

BIO:

Xian-Ming Chen, MD, is a faculty member in the Department of Microbial Pathogens and Immunity. He received graduate training in China and conducted a Sasakawa Scholarship fellowship in Japan and a second research fellowship at Mayo Clinic. His research interests focus on the regulatory role for ncRNAs in mucosal innate defense and in host-pathogen interactions. Specifically, his research group studies the expression of ncRNA genes and their role in regulation of immune responses of innate immune cells and epithelial cells in the gastrointestinal tract; interactions between gastrointestinal epithelial cells and Cryptosporidium (a long-recognized cause of chronic and life-threatening enteric disease in HIV-AIDS patients and one of the most common pathogens responsible for moderate-to-severe diarrhea in young children worldwide); and the ncRNA signatures that may link mucosal inflammation to the tumorigenesis and other infectious diseases. He served on several NIH study sections and international grant review panels.

WEBSITE: 

https://www.rushu.rush.edu/research-rush-university/departmental-research/microbial-pathogens-immunity-research/laboratory-xian-ming-chen-md