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Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines
1Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128.
Abstract:
The ability of murine recombinant gamma interferon (IFN) or lymphokines to enhance the fungicidal activity of murine pulmonary macrophages (PuM) was studied in in vitro. PuM monolayers were incubated overnight with IFN, lymph node cells (LNC) plus concanavalin A, supernatants from Con A stimulated LNC or spleen cell cultures (Con A Sup), or tissue culture medium (TCM) +/- Con A (5 micrograms/ml) or +/- lipopolysaccharide (LPS, 10 ng to 10 micrograms/ml). After treatment, culture fluids were removed and PuM were challenged for 4 h with the yeast-form Blastomyces dermatitidis or 2 h with Candida albicans. Inoculum colony forming units (CFU) of B. dermatitidis were significantly reduced by PuM treated with 1000 U/ml of IFN (25 +/- 3%), Con A Sup (25 +/- 3%) or LNC plus Con A (37-44%), but not by TCM, ConA or LPS. Candida albicans was killed by PuM treated with Con A Sup (33 +/- 8%) or LNC plus Con A (30-43%), but not by TCM, Con A, or LPS, and the activity of Con A Sup was neutralized by anti-IFN antibody. Candida albicans was not significantly killed by PuM treated with IFN doses ranging from 1 to 10(5) U/ml; nor did addition of LPS to IFN, or prolonged (3 day) treatment with IFN, result in significant killing of C. albicans by PuM. However, IFN (100 U/ml) could activate resident peritoneal macrophages for significant candidacidal activity (63%). These data indicate that PuM can be activated for fungicidal activity, and that PuM differ from resident peritoneal macrophages with regard to induction of candidacidal activity by recombinant gamma-IFN.
Insights
Murine pulmonary macrophages (PuM) treated with gamma interferon (IFN) or lymphokines showed enhanced fungicidal activity against Blastomyces dermatitidis. However, IFN did not effectively activate PuM against Candida albicans, unlike resident peritoneal macrophages.
Area of Science:
- Immunology
- Cell Biology
- Mycology
Background:
- Pulmonary macrophages (PuM) are critical for host defense against fungal infections.
- Gamma interferon (IFN) and lymphokines are known immune modulators.
- Understanding macrophage activation is key to developing antifungal strategies.
Purpose of the Study:
- To investigate the in vitro ability of murine recombinant gamma interferon (IFN) and lymphokines to enhance the fungicidal activity of murine pulmonary macrophages (PuM).
- To compare the fungicidal activity of PuM against Blastomyces dermatitidis and Candida albicans after treatment with IFN or lymphokines.
- To determine if PuM respond differently to IFN-mediated activation compared to resident peritoneal macrophages.
Main Methods:
- PuM monolayers were incubated with recombinant gamma-IFN, lymph node cells (LNC) plus concanavalin A (Con A), or supernatants from Con A-stimulated cells.
- Treated PuM were subsequently challenged with Blastomyces dermatitidis or Candida albicans.
- Fungicidal activity was assessed by measuring the reduction in colony-forming units (CFU) of the fungi.
Main Results:
- PuM treated with IFN (1000 U/ml), Con A supernatants, or LNC plus Con A showed significantly reduced Blastomyces dermatitidis CFU.
- Con A supernatants and LNC plus Con A activated PuM to kill Candida albicans, an effect neutralized by anti-IFN antibody.
- Recombinant gamma-IFN alone did not significantly enhance PuM candidacidal activity, but it did activate resident peritoneal macrophages.
Conclusions:
- Murine pulmonary macrophages can be activated for fungicidal activity against B. dermatitidis by IFN and lymphokines.
- PuM exhibit distinct responses to IFN-induced activation for candidacidal activity compared to resident peritoneal macrophages.
- These findings highlight differential activation pathways in macrophage subsets relevant to fungal immunity.