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Defective candidacidal activity of alveolar macrophages and peripheral blood monocytes from patients with chronic
A Vecchiarelli1, M Dottorini, M Puliti
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Abstract:
We investigated the in vitro candidacidal activity of alveolar macrophages (AM) and peripheral blood monocytes (PBM) from normal subjects or from patients with chronic obstructive pulmonary disease (COPD) displaying defective skin test delayed-type hypersensitivity (DTH) reactivity to seven antigens including Candida albicans. The results showed that cells from patients with COPD were significantly less effective than cells from control subjects in the killing of C. albicans. To explore whether the observed functional impairment could be reversed, interferon-gamma (IFN-gamma) was added to AM and PBM from patients with COPD, alone or in the presence of lipopolysaccharide (LPS) as a suboptimal stimulus. The cells were cultured for 24 h and then assayed for anti-Candida activity. After IFN-gamma treatment, the fungicidal activity of cells from patients with COPD was comparable to that of unstimulated AM or PBM from healthy donors. Treatment with IFN-gamma plus LPS resulted in a further enhancement in the killing of C. albicans. To gain more insight into the mechanisms involved in the modulation of killing, we evaluated the possible stimulating activity of IFN-gamma plus LPS treatment on the secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), two cytokines produced by activated macrophages and capable of stimulating natural effectors. The results showed that IFN-gamma plus LPS can indeed stimulate TNF and IL-1 secretion by AM and PBM from patients with COPD. Therefore, a precise role can reasonably be ascribed to these soluble factors in the observed augmentation of candidacidal activity as ascertained by treatment with IFN-gamma plus LPS.
Insights
Alveolar macrophages and monocytes from COPD patients show reduced Candida albicans killing. Interferon-gamma (IFN-γ) treatment restores this candidacidal activity, suggesting a potential therapeutic strategy.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Chronic obstructive pulmonary disease (COPD) is associated with impaired immune responses.
- Alveolar macrophages (AM) and peripheral blood monocytes (PBM) play crucial roles in host defense against fungal infections like Candida albicans.
Purpose of the Study:
- To investigate the in vitro candidacidal activity of AM and PBM from COPD patients.
- To determine if interferon-gamma (IFN-γ) can reverse the defective candidacidal activity in COPD patients.
Main Methods:
- Assessed in vitro candidacidal activity of AM and PBM from normal subjects and COPD patients.
- Treated COPD patient cells with IFN-γ alone or with lipopolysaccharide (LPS).
- Measured anti-Candida activity and cytokine secretion (TNF, IL-1) post-treatment.
Main Results:
- COPD patient cells exhibited significantly lower C. albicans killing compared to controls.
- IFN-γ treatment restored candidacidal activity in COPD cells to levels comparable to healthy donors.
- Combined IFN-γ and LPS treatment further enhanced fungal killing and stimulated TNF and IL-1 secretion.
Conclusions:
- Impaired candidacidal activity of macrophages and monocytes is a feature of COPD.
- IFN-γ effectively reverses this functional deficit, highlighting its potential therapeutic role.
- IFN-γ and LPS-induced cytokine production contribute to enhanced anti-Candida activity in COPD patients.