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Co-infection of macrophages modulates interferon gamma and tumor necrosis factor-induced activation against
C M Black1, L E Bermudez, L S Young
1Department of Immunology and Infectious Diseases, Palo Alto Medical Foundation, California 94301.
Abstract:
Co-infection of macrophages (M phi) with Toxoplasma gondii and Mycobacterium avium-intracellulare complex (MAC) has been observed in patients with acquired immunodeficiency syndrome (AIDS). In this study we have demonstrated that co-infected murine M phi respond differently to cytokine stimulation than M phi infected with either of the microorganisms alone. Whereas treatment with interferon gamma (IFN-gamma) activated both single and co-infected groups of M phi to kill T. gondii, treatment with TNF did not influence the rate of MAC growth in co-infected M phi, in contrast with the inhibition of growth observed in MAC-infected M phi. These results suggest that in AIDS patients suffering infection with multiple intracellular pathogens, the ability of cytokines to stimulate microbicidal or static activity in mononuclear phagocytes can be impaired by the presence of more than one of the intracellular organisms.
Insights
Co-infection with Toxoplasma gondii and Mycobacterium avium-intracellulare complex impairs macrophage responses to cytokines in AIDS patients. This suggests that multiple infections can hinder the immune system's ability to fight pathogens.
Area of Science:
- Immunology
- Cell Biology
- Infectious Diseases
Background:
- Co-infection with Toxoplasma gondii and Mycobacterium avium-intracellulare complex (MAC) is observed in acquired immunodeficiency syndrome (AIDS) patients.
- Macrophages (M phi) are key immune cells involved in combating intracellular pathogens.
Purpose of the Study:
- To investigate the differential response of co-infected murine macrophages to cytokine stimulation.
- To understand how co-infection impacts the efficacy of immune responses against T. gondii and MAC.
Main Methods:
- Murine macrophages were infected with either T. gondii or MAC alone, or co-infected with both pathogens.
- Infected and co-infected macrophages were stimulated with interferon gamma (IFN-gamma) and tumor necrosis factor (TNF).
- The microbicidal activity against T. gondii and the growth rate of MAC were assessed.
Main Results:
- IFN-gamma activated both single and co-infected macrophages to kill T. gondii.
- TNF treatment inhibited MAC growth in singly infected macrophages but had no effect on MAC growth in co-infected macrophages.
- Co-infected macrophages showed altered responses to cytokine stimulation compared to singly infected cells.
Conclusions:
- The presence of multiple intracellular pathogens can impair the ability of mononuclear phagocytes to respond effectively to cytokine stimulation.
- Cytokine efficacy in controlling intracellular infections may be compromised in individuals with co-infections, such as AIDS patients.
- These findings highlight the complex interplay between different pathogens within host immune cells.