ß2-Adrenergic Receptor Enhances the Alternatively Activated Macrophages and Promotes Biliary Injuries Caused by Helminth Infection.

The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that ß2-AR deficiency alleviates hepatobiliary damage in mice infected with C. sinensis. Moreover, ß2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice. Our in vitro results on bone marrow-derived macrophages revealed that macrophages from Adrb2-/- mice significantly decrease M2 markers and the phosphorylation of ERK/mTORC1 induced by IL-4 compared to that observed in M2 macrophages from Adrb2+/+ . This study provides a better understanding of the mechanisms by which the ß2-AR enhances type 2 immune response through the ERK/mTORC1 signaling pathway in macrophages and their role in liver fibrosis.

Opisthorchis viverrini infection causes liver and biliary cirrhosis in gerbils.

Opisthorchis viverrini infection causes many hepatobiliary diseases, including cholangiocarcinoma. Hence, the study of O. viverrini infection in humans is subject to ethical limitations, so an animal model, the Syrian hamster, is often used. O. viverrini can develop into the adult stage not only in Syrian hamsters but also in other animals, including gerbils, but until now, there has been no report on pathology and susceptibility in gerbils. The present study revealed the pathology of O. viverrini infection in gerbils through gross appearance, histopathology, and worm recovery at various time points. Gerbils were infected with 50 O. viverrini metacercariae and then sacrificed at the time of observation. The gross appearance of the liver showed micronodules at the liver surface, suggesting liver and biliary cirrhosis. Light microscopic observation was correlated to the gross appearance with cholecystitis, fatty liver changes, fibrous septa, and generalized cirrhosis. The range of worm burden fluctuated from 1 to 25 worms with large body size, which was correlated with pathology. These novel findings indicate that O. viverrini infection can cause liver and biliary cirrhosis in gerbils, depending on the worm burden, worm size, and habitat.

An inverse relationship between autoimmune liver diseases and Strongyloides stercoralis infection.

A case-control study was undertaken to describe the prevalence of Strongyloides stercoralis infection among patients with autoimmune liver diseases, such as primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). This study covered 4,117 patients who were admitted to hospitals in Okinawa, Japan, between 1988 and 2006. During this period, 538 patients had the following chronic liver diseases: PBC, AIH, PSC, chronic viral hepatitis group, and alcoholic liver disease. The other 3,579 patients who were hospitalized and underwent parasitologic tests served as controls. The frequency of S. stercoralis infection in the autoimmune liver diseases group (1.0%) was lower than that found in the control group (7.0%; P = 0.0063). None of the female patients with PBC born before 1955 had S. stercoralis infection, which was also statistically significant (P = 0.045). We hypothesized that immunomodulation by S. stercoralis infection may lower the incidence of autoimmune liver disease.

Equivocal evidence of complete carcinogenicity after repeated infection of Syrian hamsters with Opisthorchis viverrini.

The effects of repeated infection with Opisthorchis viverrini on liver lesion development in male and female Syrian hamsters were investigated over a 1-yr period. Ten monthly intragastric applications of 50, 25, 13, or 0 parasite metacercariae resulted in pronounced proliferative and inflammatory lesions involving the first- and second-order ducts in response to the presence of adult worms. Despite the development of small numbers of putative preneoplastic areas of cholangiofibrosis and morphologically altered hepatocellular foci, no neoplastic lesions were evident at sacrifice after 1 yr. The results thus suggest that parasite infestation is itself not strongly carcinogenic if at all but, rather, that it exerts a marked promoting influence on cholangiocellular and hepatocellular tumor development in the hamster via chronic irritation and increased cell turnover.

The occurrence and localization in trypanosomes and other endo-parasites of an antigen cross-reacting with mitochondrial antibodies of primary biliary cirrhosis.

1. A mitochondrion-associated antigen to primary biliary cirrhosis (PBC) in man has been shown by solid-phase radioimmunoassay and immunoautoradiography to occur in several parasitic protozoa (Trypanosoma, Plasmodium and Eimeria spp.) and in the helminths Ascaridia galli and Nippostrongylus brasiliensis. 2. Stercorarian trypanosomes and T. brucei procyclics, with more highly-developed mitochondria, appear to contain more PBC antigen than the salivarian trypomastigote, in accordance with the known mitochondrial association of the antigen. 3. Trypanosoma lewisi and A. galli gave consistently high reactivity for PBC antigen, the antigen of the former being localized predominantly to the microsomal fraction.