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Repeated exposure to bacterial lipopolysaccharide interferes with disposal of pathogenic immune complexes in mice
1Department of Pathology, Rhode Island Hospital and Brown University, Providence.
Abstract:
Patients with systemic lupus erythematosus (SLE) experience clinical flares in association with superimposed bacterial infection. To investigate whether heightened immune phenomena during the course of bacterial infections were related to abnormal disposal of immune complexes, we administered bacterial lipopolysaccharide (LPS) to C57BL/6 mice for 5 weeks. Control mice received vehicle only. We then challenged the mice with a subsaturating dose of radiolabelled immune complexes intravenously and determined the localization of immune complexes in liver, spleen and kidney. In comparison to control mice, mice exposed to LPS developed features of polyclonal B cell activation, autoimmune phenomena, delayed removal of immune complexes from the circulation, diminished liver uptake of immune complexes, and enhanced localization of immune complexes in the kidneys. The findings could not be attributed to biological processes dependent on complement concentration. Instead, interferences with Fc receptor function, or with endocytosis of immune complexes may represent likely possibilities. Thus, clinical flares in patients with SLE, in the presence of a superimposed infection, may result from enhanced localization of immune complexes in organs due to altered mechanisms of their disposal.
Insights
Bacterial infections may worsen systemic lupus erythematosus (SLE) flares by disrupting how the body clears immune complexes. This leads to immune complexes accumulating in organs like the kidneys, potentially triggering autoimmune responses.
Area of Science:
- Immunology
- Autoimmunity
- Pathophysiology
Background:
- Systemic lupus erythematosus (SLE) patients often experience flares during bacterial infections.
- The mechanism linking infection, immune complex clearance, and SLE flares is not fully understood.
Purpose of the Study:
- To investigate if bacterial infections alter immune complex disposal in a mouse model.
- To determine the impact of bacterial lipopolysaccharide (LPS) exposure on immune complex localization and clearance.
Main Methods:
- C57BL/6 mice were administered bacterial lipopolysaccharide (LPS) or vehicle for 5 weeks.
- Mice were subsequently injected with radiolabeled immune complexes.
- Localization of immune complexes in the liver, spleen, and kidneys was quantified.
Main Results:
- LPS-exposed mice showed polyclonal B cell activation and autoimmune phenomena.
- Immune complex clearance from circulation was delayed in LPS-exposed mice.
- Diminished liver uptake and enhanced kidney localization of immune complexes were observed in LPS-exposed mice.
- Findings were independent of complement concentration, suggesting Fc receptor or endocytosis interference.
Conclusions:
- Superimposed bacterial infections may impair immune complex disposal in SLE.
- Altered immune complex localization, particularly in the kidneys, could contribute to SLE flares.
- Interference with Fc receptor function or endocytosis is a potential mechanism.