Proinflammatory effects of environmental cadmium boost resistance to opportunistic pathogen Aspergillus fumigatus: Implications for sustained low-level pulmonary inflammation?
2021
Authors:
Kulaš, JelenaTucović, Dina
Zeljković, Milica
Popović, Dušanka
Popov Aleksandrov, Aleksandra
Ukropina, Mirela
Cakić Milošević, Maja
Glamočlija, Jasmina
Kataranovski, Milena
Mirkov, Ivana
Document Type:
Article (Published version)
,
© 2020 Elsevier B.V.
Metadata
Show full item recordAbstract:
Cadmium (Cd) is one of the most toxic environmental heavy metals to which the general population is exposed mainly via the oral route. Owing to its immunomodulatory potential, orally acquired Cd affects antimicrobial immune defense in several organs, including the lungs. While there are data concerning Cd and viral and bacterial pulmonary infections, effects on fungal infections are not studied yet. In the present study, the effect of the Cd (5 mg/L for 30 days, in drinking water, the average daily Cd intake 0.641 ± 0.089 mg/kg) on the immune response of rats to pulmonary A. fumigatus infection was examined. Data obtained showed that orally acquired cadmium does not affect the elimination of the fungus in immunocompetent rats owing to the preservation of some aspects of innate immune responses (lung leukocyte infiltration and NBT reduction) and an increase in other (increased numbers of mucus-producing goblet cells, MPO release). Cd does not affect an IFN-γ response in lung leukocytes during the infection (despite suppression of cytokine production in cells of lung-draining lymph nodes), while it stimulates IL-17 and suppresses IL-10 response to the fungus. As a result, the elimination of the fungus occurs in a milieu with the prevailing proinflammatory response in Cd-exposed animals that preserved fungal elimination from the lungs, though with more intense injury to the lung tissue. Therefore, the proinflammatory microenvironment in the lungs created by Cd that sustains inflammatory/immune response to the fungus to which humans are exposed for a lifetime, raises a concern of orally acquired Cd as a risk factor for the development of chronic low-grade pulmonary inflammation.
Keywords:
Aspergillus fumigatus; Enhanced lung inflammation; Environmental health risk; Oral cadmium administrationSource:
Toxicology, 2021, 447, 152634-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.1016/j.tox.2020.152634
ISSN: 0300-483X
PubMed: 33197509
WoS: 000600692500009
Scopus: 2-s2.0-85096483025
URI
https://linkinghub.elsevier.com/retrieve/pii/S0300483X20302730https://radar.ibiss.bg.ac.rs/handle/123456789/4033