Persistent salmonellosis causes pancreatitis in a murine model of infection.
Pancreatitis, a known risk factor for the development of pancreatic ductal adenocarcinoma, is a serious, widespread medical condition usually caused by alcohol abuse or gallstone-mediated ductal obstruction. However, many cases of pancreatitis are of an unknown etiology. Pancreatitis has been linked to bacterial infection, but causality has yet to be established. Here, we found that persistent infection of mice with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) was sufficient to induce pancreatitis reminiscent of the human disease. Specifically, we found that pancreatitis induced by persistent S. Typhimurium infection was characterized by a loss of pancreatic acinar cells, acinar-to-ductal metaplasia, fibrosis and accumulation of inflammatory cells, including CD11b+ F4/80+, CD11b+ Ly6Cint Ly6G+ and CD11b+ Ly6Chi Ly6G- cells. Furthermore, we found that S. Typhimurium colonized and persisted in the pancreas, associated with pancreatic acinar cells in vivo, and could invade cultured pancreatic acinar cells in vitro. Thus, persistent infection of mice with S. Typhimurium may serve as a useful model for the study of pancreatitis as it relates to bacterial infection. Increased knowledge of how pathogenic bacteria can cause pancreatitis will provide a more integrated picture of the etiology of the disease and could lead to the development of new therapeutic approaches for treatment and prevention of pancreatitis and pancreatic ductal adenocarcinoma.
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, United States of America; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America; Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Kathleen E
KE
DelGiorno
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, United States of America; Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, United States of America.
Jason W
JW
Tam
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America; Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Jason C
JC
Hall
Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Gangadaar
G
Thotakura
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, United States of America; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America; Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Howard C
HC
Crawford
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, United States of America; Department of Pathology, Stony Brook University, Stony Brook, New York, United States of America; Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, United States of America.
Adrianus W M
AW
van der Velden
D061354:Acinar Cells / Q000382:microbiology / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008070:Lipopolysaccharides; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000382:microbiology / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology* / Q000473:pathology; D012481:Salmonella Infections, Animal / Q000150:complications* / Q000473:pathology; D012486:Salmonella typhimurium / Q000502:physiology
D008070:Lipopolysaccharides