Avan Antia

Program: Molecular Microbiology and Microbial Pathogenesis

Current advisor: Siyuan Ding, PhD

Undergraduate university: University of Maryland-College Park, 2016

Enrollment year: 2019

Research summary
Investigating the role of intestinal M cells in Rotavirus enteric infection

Rotavirus (RV) is the leading cause of viral gastroenteritis related morbidity and mortality in young children worldwide. Despite years of RV research and the development of multiple approved mucosal vaccines, RV continues to be an important cause of pediatric illness in many lower to middle income nations. As the field of mucosal immunity flourishes, it is important to update our understanding of RV infection and immunity in this new context. The intestinal mucosal barrier is protected by gut-associated lymphoid tissue, which involves a complex set of cellular players. One such player is the M cell, a highly specialized, polarized epithelial cell type which samples luminal antigen and delivers it to a pocket of lymphocytes, thus initiating an immune response and leading to the production of secretory IgA. It is agreed that M cells contribute to immunosurveillance of enteric bacteria and protein antigens, however, it is not known what role M cells play in the context of enteric viral infection. In this study, we use RV as a model enteric virus to probe the role of M cells in viral clearance, specific IgA production, and protection from reinfection. RV is a useful tool to study protective immunity in vivo, as RV infection in mice induces RV-specific IgA, which correlates with clearance and leads to lifetime protection against reinfection, allowing us to study factors that may disrupt the development of sterilizing immunity. Using a conditional M cell knockout mouse model, we are able to investigate the interactions between this relatively rare cell type and enteric viral infection.

Thus far, we have found that M cells may be redundant for IgA production in response to virulent murine RV infection. However, upon oral vaccination with a low dose of live-attenuated RV, M cell deficient mice fail to produce intestinal anti-RV IgA and are susceptible to challenge by a virulent RV strain, compared to fully protected control mice. Through these studies, we are uncovering the interactions between a ubiquitous enteric pathogen and a unique, and rather understudied, host cell type. This work will improve our understanding of the protective role of M cells against enteric virus infection and move us closer towards developing better mucosal vaccines.

Graduate publications
Antia A, Alvarado DM, Ding S, Ciorba MA. 2022 Adding Fuel to The Fire? A Role of Intraepithelial Lymphocytes in Enteric Immune Responses to SARS-CoV-2 Infection. Gastroenterology, ():S0016-5085(21)04120-2. PMCID: PMC8694654

Antia A, Pinski AN, Ding S. 2022 Re-Examining Rotavirus Innate Immune Evasion: Potential Applications of the Reverse Genetics System. mBio, ():e0130822

Antia A, Alvarado DM, Zeng Q, Casorla-Perez LA, Davis DL, Sonnek NM, Ciorba MA, Ding S. 2022 SARS-CoV-2 Omicron (BA.1) variant infection of human colon epithelial cells. Viruses, 16(4):634. PMCID: PMC11055019