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Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Influence of tumour condition on the macrophage activity in Candida albicans infection
J Venturini1, M R de Camargo, M C Félix
1Experimental Immunopathology Laboratory, Department of Biological Sciences, College of Sciences, Sao Paulo State University-UNESP, Bauru, São Paulo, Brazil.
Abstract:
To better understand the interactions between opportunistic fungi and their hosts, we investigated hydrogen peroxide (H2O2), nitric oxide and TNF-alpha production by peritoneal macrophages from Ehrlich tumour-bearing mice (TBM) during microbial infections. For this purpose, TBM at days 7, 14 and 21 of tumour progression were inoculated intraperitoneally with C. albicans and evaluated after 24 and 72 h. We observed that TBM showed significant increases in H2O2, TNF-alpha levels and fungal clearance at day 7 after C. albicans infection. However, as the tumour advanced, there was a progressive decline in the release of H2O2 and TNF-alpha that was paired with the dissemination of C. albicans. These results demonstrate that protective macrophage activities against Candida albicans are limited to the initial stages of tumour growth; continued solid tumour growth weakened the macrophage response and as a consequence, weakened the host's susceptibility to opportunistic infections.
Insights
Tumor progression in mice weakens macrophage response to Candida albicans. Early tumor growth enhances immune activity, but later stages increase susceptibility to opportunistic fungal infections.
Area of Science:
- Immunology
- Mycology
- Cancer Biology
Background:
- Opportunistic fungal infections pose risks to immunocompromised individuals, including cancer patients.
- Macrophages play a crucial role in host defense against microbial pathogens.
Purpose of the Study:
- To investigate the impact of tumor progression on macrophage function and host defense against Candida albicans.
- To analyze the production of key immune mediators like hydrogen peroxide (H2O2) and TNF-alpha by macrophages in tumor-bearing mice.
Main Methods:
- Peritoneal macrophages from Ehrlich tumor-bearing mice (TBM) at different stages of tumor growth (days 7, 14, 21) were infected with Candida albicans.
- Production of H2O2, nitric oxide, and TNF-alpha by macrophages was measured.
- Fungal clearance and dissemination were assessed.
Main Results:
- At early tumor stages (day 7), TBM showed increased H2O2 and TNF-alpha production, leading to enhanced fungal clearance.
- As tumors progressed (days 14, 21), macrophage production of H2O2 and TNF-alpha significantly declined.
- This decline in immune response correlated with increased Candida albicans dissemination.
Conclusions:
- Macrophage-mediated defense against Candida albicans is effective only during the initial phases of tumor development.
- Advanced tumor growth impairs macrophage function, compromising the host's ability to control opportunistic fungal infections.
- Understanding these dynamics is crucial for developing therapeutic strategies against fungal infections in cancer patients.
