Efekat oralne primene kadmijum-hlorida na imunski odgovor u plućima pacova u fiziološkim i patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Аspergillus fumigatus
Effects of oral cadmium-chloride intake on immune response in the lungs of rats in physiological and pathophysiological conditions of infection with opportunistic fungus Aspergillus fumigatus
Abstract:
Cadmium is one of the most toxic heavy metals to which the general population is exposed mostly through contaminated food. Although cadmium taken orally is known to be deposited in the lungs, there is little evidence of an immune response in the lungs to this metal. The immunomodulatory effect of cadmium reaching the body orally (30 days in drinking water) was examined under physiological conditions by measuring changes in cellular and molecular mechanisms of the immune response to non-lethal metal doses (5 and 50 mg/l) in rats and pathophysiological conditions of infection caused by opportunistic fungus Aspergillus fumigatus. The role of the aryl hydrocarbon receptor (AhR) in cadmium immunotoxicity was also investigated. Under physiological conditions, the presence of cadmium in the lungs caused oxidative stress, inflammation, and tissue damage. Cadmium exhibited differential effects on lung leukocyte activity (unchanged production of reactive oxygen species and nitrogen, inhibition of IL-1β and TNF, stimulation of MPO and IFN-γ) with cadmium effects on cytokine production mediated by AhR activation. In the pathophysiological conditions of infection caused by A. fumigatus, cadmium led to more efficient removal of fungus from tissues (directly suppressing fungal growth, increasing goblet cell count and mucus production, and leding to more intense T-cell differentiation towards Th17 T-cells in regional lymph nodes and their greater activity in lung tissue). A more intense response to the fungus in individuals who drank cadmium caused greater damage to lung tissue. The proinflammatory microenvironment in the lungs established by cadmium makes this heavy metal a risk factor for the development of low-grade chronic inflammation in the lungs, which could affect the sensitivity of the organism in various pathophysiological conditions.
Keywords:
Aspergillus fumigatus; Oral cadmium intake; DA rats; Lung immune system; Aryl hydrocarbon receptorSource:
Faculty of Biology, University of Belgrade, 2022, 1-69Funding / projects:
- Immunomodulatory effects of environmental xenobiotics and biotic factors on the populations of mouse-like rodents (RS-MESTD-Basic Research (BR or ON)-173039)