Microbial Adjuvant and Autoimmunity

Abstract

Definite lesions in the exocrine pancreas were produced when SMA mice were immunized eight times at intervals of 30 days with a mixture of extract of pooled pancreas from syngeneic mice and the capsular polysaccharide of Klebsiella pneumoniae type 1 Kasuya strain (CPS-K), whereas no pancreatic lesions were produced in mice given CPS-K alone or pancreatic extract alone. The typical histological changes were characterized by infiltration with lymphocytes, plasma cells, and other mononuclear cells, degeneration and lysis of the acinar cells, destruction of the lobular architecture, and replacement by fatty tissue and fibrous connective tissue. The endocrine islets were well preserved. No specific histological changes were produced in the organs other than the pancreas in these mice. Most of mice immunized with pancreatic extract mixed with CPS-K produced serum precipitins to syngeneic pancreatic antigens. However, severe pancreatic lesions were also produced in mice showing no definite precipitin production.Occurrence of circulating antibodies to the pancreas has been described in chronic pancreatitis and other pancreatic diseases (3,4,(18)(19)(20)(21). It was also reported that lymphocytes were sensitized specifically with the organ-specific human pancreatic antigens in most cases of chronic pancreatitis in man (16,17,21), and that antinuclear factors were detected in the serum of most patients with acute and chronic pancreatitis of unknown etiology (13). These results suggest that immunological mechanisms are involved in the development of some types of chronic pancreatitis in man. It was reported that acute interstitial pancreatitis and elevation in the serum amylase values were induced after injection of rabbit anti-guinea pig pancreas antiserum into guinea pigs (14). Rabbit anti-dog pancreas antiserum was also found to induce serum amylase increases within 4 days when administered passively to dogs, although the histological appearance of the 945

Intestinal Dysbiosis and Autoimmune Pancreatitis

“…These data strongly suggest that gut colonization of K. pneumoniae increases the sensitivity of AIP through activation of pDCs which produce IFN-a and IL-33. Pathogenicity of K. pneumoniae was also reported in a previous report showing that immunization with a mixure of extract of pooled pancreas from syngeneic mice and the capsular polysaccharide of K. pneumoniae led to the development of chronic fibroinflammatory responses in the pancreas (37). Collectively, these studies strongly support involvement of intestinal dysbiosis in the development of AIP.…”

Commensal Flora, is it an Unwelcomed Companion as a Triggering Factor of Autoimmune Pancreatitis?

“…It is worth mentioning that long before the concept of AIP was proposed as a definite disease entity, Yamaki et al (1980) had established inflammation of the exocrine pancreas using syngeneic pancreatic antigens. Repeated injection of pancreatic extract from syngeneic mice mixed with capsular polysaccharide (CPS) of the Klebsiella pneumoniae type 1 Kasuya strain (CPS-K), as an adjuvant, caused pathological alteration in the pancreas, consistent with infiltration by lymphocytes, plasma cells and mononuclear cells, degradation and lysis of the acinar cells, and destruction of the lobular architecture, replacement of fatty tissue and fibrous connective tissue and anti-pancreas antibody production.…”

“…No histological changes were observed in tissues other than the pancreas and either CPS-K or the pancreatic extract alone were insufficient to induce inflammation in the pancreas. K. pneumoniae is one of the commonly found bacteria in Enterobacteriaceae (Yamaki et al, 1980), the natural habitat of the intestinal tract, and it is an opportunistic bacterium. The CPS is a voluminous outer layer and is involved in protection against complement deposition that occurs mainly in the inhibition of macrophage phagocytosis (Evrard et al, 2010).…”

Characterization of Autoantigens Relevant to Autoimmune Ophthalmitis and Thyroiditis in Mice Immunized with the Syngeneic Tissue Extracts and Klebsiella O3 Lipopolysaccharide

“…Our previous studies have shown that the polysaccharide-rich fraction isolated from the culture supernatant of Klebsiella pneumoniae strain Kasuya (O3 : K1) exhibits a strong adjuvant effect on antibody response of mice to various antigens and the substance responsible for this strong adjuvant effect is Klebsiella O3 lipopolysaccharide (KO3 LPS) (4). We have established autoimmune diseases in various organs of mice by injecting syngeneic tissue extracts together with KO3 LPS (5,6,8,9,18). Especially, our experimental models for autoimmune ophthalmitis and thyroiditis showed high precipitin responses to syngeneic eyeball extract and thyroid extract which are normally nonimmunogenic (8) and produced characteristic severe lesions (9,19).…”

“…We have established autoimmune diseases in various organs of mice by injecting syngeneic tissue extracts together with KO3 LPS (5,6,8,9,18). Especially, our experimental models for autoimmune ophthalmitis and thyroiditis showed high precipitin responses to syngeneic eyeball extract and thyroid extract which are normally nonimmunogenic (8) and produced characteristic severe lesions (9,19).…”