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Activation of murine polymorphonuclear neutrophils for fungicidal activity by recombinant gamma interferon
Abstract:
Recombinant murine gamma-interferon (IFN) was tested for its ability to enhance murine polymorphonuclear neutrophil (PMN) fungicidal activity in vitro. PMNs, elicited by intraperitoneal injection of thioglycollate 4 hr prior to collection, were treated with 0.00003-300,000 units of IFN per milliliter for 1 hr prior to challenge with yeast form Blastomyces dermatitidis. These PMNs were not fungicidal for Blastomyces in the absence of IFN; significant enhancement of PMN fungicidal activity by IFN treatment occurred in a dose-dependent manner with maximal enhancement observed at 30,000 U/ml (21% killing). Pretreatment of IFN with rabbit anti-IFN antiserum before addition to PMNs eliminated the enhancement of fungicidal activity by effective doses of IFN. PMN fungicidal activity against phagocytizable Candida albicans was significantly (P less than .001) higher (71.3 +/- 17.4%) than against B. dermatitidis. Candidacidal activity was not significantly enhanced by IFN treatment of PMNs. Exogenously added lipopolysaccharide, at levels corresponding to those found in this preparation of IFN, did not activate PMNs for enhanced fungicidal capacity. These data indicate a stimulatory role for IFN in the killing of B. dermatitidis by PMNs, suggesting that IFN is an active component of the communication between T lymphocytes and PMNs with respect to antimicrobial resistance. They suggest a natural role for IFN in host defense against blastomycosis and other fungal infections, and a possible therapeutic use for exogenous IFN in fungal disease.
Insights
Recombinant gamma-interferon (IFN) significantly boosts mouse neutrophil (PMN) ability to kill Blastomyces dermatitidis in vitro. This enhancement, dose-dependent, suggests IFN
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Murine polymorphonuclear neutrophils (PMNs) are crucial for innate immunity.
- Fungal infections like blastomycosis pose significant health challenges.
- The role of gamma-interferon (IFN) in modulating PMN fungicidal activity requires further elucidation.
Purpose of the Study:
- To investigate the in vitro effect of recombinant murine gamma-interferon (IFN) on the fungicidal activity of murine polymorphonuclear neutrophils (PMNs).
- To determine the dose-dependent response of PMNs to IFN when challenged with Blastomyces dermatitidis.
- To explore the specificity of IFN's effect on PMN fungicidal activity against different fungal species.
Main Methods:
- Murine PMNs were elicited and treated with varying concentrations of recombinant murine IFN.
- Treated PMNs were challenged with yeast-form Blastomyces dermatitidis in vitro.
- IFN's effect was assessed by measuring PMN fungicidal activity.
- Control experiments included using anti-IFN antiserum and lipopolysaccharide.
Main Results:
- IFN treatment significantly enhanced PMN fungicidal activity against Blastomyces dermatitidis in a dose-dependent manner, with maximal effect at 30,000 U/ml.
- Anti-IFN antiserum abolished the enhancing effect of IFN, confirming its specificity.
- IFN did not significantly enhance PMN fungicidal activity against Candida albicans.
- Exogenous lipopolysaccharide did not induce similar enhancement, ruling out contamination as a factor.
Conclusions:
- Gamma-interferon (IFN) plays a stimulatory role in the killing of Blastomyces dermatitidis by murine polymorphonuclear neutrophils (PMNs).
- IFN acts as a mediator between T lymphocytes and PMNs, contributing to antimicrobial resistance against fungal pathogens.
- These findings suggest a natural role for IFN in host defense against blastomycosis and other fungal infections, with potential therapeutic applications.