Specific strains of Streptococcus mutans, a pathogen of dental caries, in the tonsils, are associated with IgA nephropathy

Seigo Ito,Kazuhiko Nakano,Michiyo Matsumoto-Nakano,Masatoshi Otsugu,Ryota Nomura,Yasuyuki Nagasawa,Kaoruko Wato,Shuhei Naka,Hiroo Kumagai,Taro Misaki,Naoki Oshima

doi:10.1038/s41598-019-56679-2

Abstract

Streptococcus mutans is known to be a major causative agent of dental caries, and strains expressing the cell surface collagen-binding Cnm protein contribute to the development of several systemic diseases. A relationship between tonsillar immunity and glomerulonephritis has been recognized in IgA nephropathy (IgAN), and specific pathogens may have effects on tonsillar immunity (mucosal immunity). Here, we present findings showing a relationship between the presence of Cnm-positive S. mutans strains in the tonsils of IgAN patients and IgAN condition/pathogenesis. Analyses of tonsillar specimens obtained from patients with IgAN (n = 61) and chronic tonsillitis (controls; n = 40) showed that the Cnm protein-positive rate was significantly higher in IgAN patients. Among IgAN patients, the tonsillar Cnm-positive group (n = 15) had a significantly higher proportion of patients with high urinary protein (>1.5 g/gCr) and lower serum albumin level than the Cnm-negative group (n = 46). Additionally, Cnm protein and CD68, a common human macrophage marker, were shown to be merged in the tonsils of IgAN patients. These findings suggest that Cnm-positive S. mutans strains in the tonsils may be associated with severe IgAN.

Highlights

Streptococcus mutans is known to be a major causative agent of dental caries, and strains expressing the cell surface collagen-binding Cnm protein contribute to the development of several systemic diseases
To confirm a specific reaction of Cnm antiserum to Cnm-positive S. mutans in the tonsil tissues, immunoperoxidase staining for Cnm was performed with serial tonsillar sections using Cnm antiserum either unsaturated or saturated with recombinant Cnm protein, which showed that saturation with rCnm protein diminished tonsillar staining by Cnm antiserum (Fig. 1C)
Our findings showed that the Cnm-positive area/total tonsillar area ratio was significantly higher in IgA nephropathy (IgAN) patients than in the control group (Table 1)

Summary

Introduction

Streptococcus mutans is known to be a major causative agent of dental caries, and strains expressing the cell surface collagen-binding Cnm protein contribute to the development of several systemic diseases. A relationship between tonsillar immunity and glomerulonephritis has been recognized in IgA nephropathy (IgAN), and specific pathogens may have effects on tonsillar immunity (mucosal immunity). We present findings showing a relationship between the presence of Cnm-positive S. mutans strains in the tonsils of IgAN patients and IgAN condition/pathogenesis. Analyses of tonsillar specimens obtained from patients with IgAN (n = 61) and chronic tonsillitis (controls; n = 40) showed that the Cnm protein-positive rate was significantly higher in IgAN patients. Cnm protein and CD68, a common human macrophage marker, were shown to be merged in the tonsils of IgAN patients. These findings suggest that Cnm-positive S. mutans strains in the tonsils may be associated with severe IgAN. Periodontitis-related bacteria, have been referred to as the causal antigens or exacerbation factors in the pathogenesis of the disease[14,15,16,17,18]

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Conclusion