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Actinobacillus pleuropneumoniae-induced thymic lesions in mice and pigs
D L Stine1, M J Huether, R A Moxley
1Department of Veterinary Science, University of Nebraska-Lincoln 68583-0905.
Abstract:
Actinobacillus pleuropneumoniae produces several hemolysins/cytotoxins that may be important in the pathogenesis of acute lesions. Little is known, however, about the role of these virulence factors in chronic disease or the carrier state. We investigated the effects of live bacterial infection and transthoracic injection of a sterile culture supernatant on primary lymphoid organs and lymphocyte populations. Transthoracic inoculation of mice or intranasal inoculation of pigs with virulent A. pleuropneumoniae serotypes 1 and 7 induced thymic cortical lymphoid necrosis. These lesions were reproduced in mice by transthoracic injection of a concentrated sterile culture supernatant. The cytotoxic effect of this culture supernatant was also demonstrated in vitro by using a tetrazolium dye reduction assay. Both porcine and murine thymic lymphocytes as well as splenic T lymphocytes were susceptible to the toxin. Porcine convalescent serum, but not preimmune serum, prevented thymic lesions and neutralized the in vitro cytotoxic effect of the culture supernatant on murine thymic lymphocytes. Thymic lesions also were reproduced in mice by using purified lipopolysaccharide (LPS) from Escherichia coli O111:B4; however, LPS had no in vitro cytotoxic effect on either porcine or murine thymic lymphocytes. These results suggest that secreted A. pleuropneumoniae toxin(s) is capable of affecting host T-lymphocyte populations and may affect host immune function.
Insights
Actinobacillus pleuropneumoniae toxins damage thymic and splenic T lymphocytes, potentially impacting host immune function. This study reveals secreted toxins, not LPS, are responsible for these cytotoxic effects.
Area of Science:
- Veterinary Immunology
- Bacterial Pathogenesis
- Toxinology
Background:
- Actinobacillus pleuropneumoniae virulence factors are implicated in acute disease, but their role in chronic infections and carrier states is unclear.
- Understanding the impact of bacterial toxins on host lymphoid organs is crucial for elucidating disease pathogenesis.
Purpose of the Study:
- To investigate the effects of Actinobacillus pleuropneumoniae infection and its secreted toxins on primary lymphoid organs and lymphocyte populations.
- To determine the susceptibility of porcine and murine lymphocytes to bacterial toxins and lipopolysaccharide (LPS).
Main Methods:
- Transthoracic inoculation of mice and intranasal inoculation of pigs with virulent A. pleuropneumoniae serotypes.
- Transthoracic injection of sterile culture supernatant and purified LPS from Escherichia coli O111:B4.
- In vitro cytotoxic assays using tetrazolium dye reduction and assessment of serum neutralization.
Main Results:
- A. pleuropneumoniae infection and its secreted toxins induced thymic cortical lymphoid necrosis in mice and pigs.
- Porcine and murine thymic lymphocytes and splenic T lymphocytes were susceptible to the secreted toxin in vitro.
- Porcine convalescent serum neutralized the cytotoxic effects, while E. coli LPS did not exhibit in vitro cytotoxicity.
Conclusions:
- Secreted toxins from A. pleuropneumoniae directly affect host T-lymphocyte populations, specifically thymic and splenic lymphocytes.
- These bacterial toxins may play a significant role in modulating host immune function during infection.
- The findings highlight the importance of secreted toxins as virulence factors in A. pleuropneumoniae pathogenesis.