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Primary biliary cirrhosis in the mouse: induction by human mycoplasma-like organisms
L Johnson1, E Wirostko, W Wirostko
1Department of Pathology, Columbia-Presbyterian Medical Center, New York, NY 10032.
Abstract:
Human intraocular and orbital chronic inflammatory disease with autoimmune features has been reported to be caused by mycoplasma-like organisms (MLO). MLO are intracellular cell-wall deficient pathogenic bacteria, closely related to rickettsia, with a characteristic ultrastrural pleomorphic tubulo-spherical and filamentous appearance. No culture system has been developed for MLO and diagnosis of MLO disease is made by detecting these bacteria within infected cells using a transmission electron microscope. In human MLO ocular and orbital disease the organisms are found in parasitized leucocytes at the disease site. Inoculation of human MLO into mouse eyelids produces a high incidence of orbital and introcular disease. MLO disseminate to produce randomly distributed lethal systemic disease with infected leucocytes found in all disease sites and with similar histologic features in all disease sites. Microvasculitis is the initial lesion. Disease progression results in lysis of vascular and parenchymal structures, stromal lymphocytic infiltrates, granulomas, and fibrosis. This report describes the hepatic portal chronic progressive inflammatory disease in 11 of 100 of those mice versus 0 in 200 controls. MLO parasitized portal leucocytes are present in all 11 inflamed livers versus 0 in 5 control livers (P less than 0.05). The resemblance of the animal liver disease induced by MLO to human primary biliary cirrhosis and rifampin treatment of MLO disease are discussed.
Insights
Mycoplasma-like organisms (MLO) cause chronic inflammatory eye disease in humans. This study shows MLO also induce progressive liver inflammation in mice, resembling human biliary cirrhosis.
Area of Science:
- Microbiology
- Immunology
- Ophthalmology
Background:
- Mycoplasma-like organisms (MLO) are implicated in human intraocular and orbital inflammatory diseases.
- MLO are intracellular, cell-wall deficient bacteria, challenging to culture and diagnose.
- Current diagnosis relies on transmission electron microscopy to detect MLO within infected cells.
Purpose of the Study:
- To investigate the pathogenic potential of MLO in a murine model.
- To characterize the systemic effects of MLO infection, including ocular, orbital, and hepatic manifestations.
- To explore the potential link between MLO-induced liver disease and human primary biliary cirrhosis.
Main Methods:
- Inoculation of human MLO into mouse eyelids to induce disease.
- Histopathological examination of ocular, orbital, and systemic tissues.
- Microscopic analysis of liver tissues to identify MLO and inflammatory markers.
Main Results:
- MLO inoculation caused high incidence of orbital and intraocular disease in mice.
- Systemic dissemination of MLO was observed, with infected leucocytes in all disease sites.
- Chronic progressive hepatic portal inflammatory disease developed in 11% of infected mice, absent in controls.
- MLO-parasitized portal leucocytes were found in inflamed livers, suggesting a direct role in hepatic pathology.
Conclusions:
- MLO can induce severe systemic disease, including chronic progressive liver inflammation in mice.
- The observed murine liver pathology shares similarities with human primary biliary cirrhosis.
- These findings highlight MLO as a significant pathogen with potential implications for autoimmune liver diseases.