Digestion of killed Paracoccidioides brasiliensis by neutrophils.

Section of Immunology I, Instituto de Biomedicina, Central University of Venezuela, Caracas.
Mycopathologia (Impact Factor: 1.55). 05/1989; 106(1):53-8. DOI: 10.1007/BF00436927
Source: PubMed

ABSTRACT We previously described an in vitro assay showing that neutrophils (PMNs) from patients with paracoccidioidomycosis (PARA) have a specific digestive deficiency against suspensions of live Paracoccidioides brasiliensis. We now report that this defect is equally detectable against autoclaved, but not Amphotericin B-killed P. brasiliensis. The use of autoclaved suspensions facilitates the use of our in vitro assay. It might allow the development of an in vitro intradermal test for digestion of fungi. Differential digestive ability of phagocytes against live (or autoclaved) and Amphotericin-B killed fungi is of conceptual interest. It may be relevant in understanding therapeutic effect of Amphotericin B.

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    ABSTRACT: Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.
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