Contributions of Streptococcus mutans Cnm and PA antigens to aggravation of non-alcoholic steatohepatitis in mice.
Streptococcus mutans, a major pathogen of dental caries, can cause infective endocarditis after invading the bloodstream. Recently, intravenous administration of specific S. mutans strains was shown to aggravate non-alcoholic steatohepatitis (NASH) in a mouse model fed a high-fat diet. Here, we investigated the mechanism of this aggravation in a NASH mouse model by focusing on the S. mutans cell surface collagen-binding protein (Cnm) and the 190-kDa protein antigen (PA). Mice that were intravenously administered a S. mutans strain with a defect in Cnm (TW871CND) or PA (TW871PD) did not show clinical or histopathological signs of NASH aggravation, in contrast to those administered the parent strain TW871. The immunochemical analyses demonstrated higher levels of interferon-γ and metallothionein expression in the TW871 group than in the TW871CND and TW871PD groups. Analysis of bacterial affinity to cultured hepatic cells in the presence of unsaturated fatty acids revealed that the incorporation rate of TW871 was significantly higher than those of TW871CND and TW871PD. Together, our results suggest that Cnm and PA are important cell surface proteins for the NASH aggravation caused by S. mutans adhesion and affinity for hepatic cells.
Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
Shuhei
S
Naka
Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
Rina
R
Hatakeyama
Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yukiko
Y
Takashima
Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Michiyo
M
Matsumoto-Nakano
Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
Ryota
R
Nomura
Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
Kazuhiko
K
Nakano
D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001422:Bacterial Adhesion; D002352:Carrier Proteins / Q000276:immunology*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D022781:Hepatocytes / Q000382:microbiology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000276:immunology / Q000382:microbiology*; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology*; D013295:Streptococcus mutans / Q000276:immunology*
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D002352:Carrier Proteins; C488758:Cnm protein, Streptococcus mutans; D005227:Fatty Acids