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Experimental infection of immunocompromised mice with Achromobacter xylosoxidans
Abstract:
The natural resistance of mice to Achromobacter (A.) xylosoxidans was decreased to 1/80 by a single dose of 250 mg of cylophosphamide (CY) per kg intraperitoneally. When mice were infected with 1 X 10(9) A. xylosoxidans, the numbers of organisms in the liver, spleen, kidneys, lungs and heart blood reached to more than 10(6) per g at 6 hr after infection, and then decreased to less than 10(4) at 96 hr after infection. However, in the CY-treated mice, the numbers of organisms in these organs began to increase rapidly at 6 hr after infection and exceeded 10(9) per g at 48 hr when the mice died. Seventeen of 18 immunocompromised mice and 23 of 24 normal mice which were infected with 1 to 2 X 10(9) organisms of A. xylosoxidans, respectively, were still living until 4 weeks after infection when they were killed and examined. Thirteen of the 33 surviving mice which were examined for bacteriological assay were chronically infected with A. xylosoxidans, some in the spleen, others in the kidney, lung, brain and/or heart blood but none were infected in the liver. Most of the infected and surviving mice had produced an antibody against A. xylosoxidans and its titer was higher in the bacteriologically "cured" group than in the chronically infected one. All surviving mice were resistant to the 2nd challenge with a lethal dose of A. xylosoxidans even when they received an effective dose of CY. The surviving mice showed activated cellular immunity and rather depressed humoral immunity as compared with normal mice or the mice which were infected with killed A. xylosoxidans.
Insights
Cyclophosphamide (CY) significantly reduced mouse resistance to Achromobacter xylosoxidans infection. Surviving mice developed chronic infections but gained resistance to lethal re-challenge, indicating complex immune responses.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Achromobacter xylosoxidans is an opportunistic pathogen.
- Understanding host-pathogen interactions and immune responses is crucial for managing infections.
- Cyclophosphamide (CY) is an immunosuppressive agent used to study immune function.
Purpose of the Study:
- To investigate the impact of cyclophosphamide (CY) on mouse susceptibility to Achromobacter xylosoxidans.
- To characterize the course of A. xylosoxidans infection in immunocompromised and normal mice.
- To evaluate the immune response and long-term outcomes in surviving mice.
Main Methods:
- Mice were treated with cyclophosphamide (CY) to induce immunosuppression.
- Mice were infected with varying doses of Achromobacter xylosoxidans.
- Bacterial load in organs, survival rates, antibody production, and cellular/humoral immunity were assessed.
Main Results:
- CY treatment significantly decreased natural resistance to A. xylosoxidans.
- CY-treated mice exhibited rapid bacterial proliferation and mortality.
- A significant proportion of surviving mice (both normal and immunocompromised) developed chronic A. xylosoxidans infections.
- Surviving mice developed antibodies against A. xylosoxidans and were resistant to lethal re-infection, even with CY treatment.
- Long-term survivors displayed activated cellular immunity and suppressed humoral immunity.
Conclusions:
- Cyclophosphamide (CY) exacerbates Achromobacter xylosoxidans infections in mice.
- Infection with A. xylosoxidans can lead to chronic infections and long-term immunity in surviving mice.
- Activated cellular immunity plays a role in resistance to re-infection despite immunosuppression.