Abstract
Chronic ethanol consumption is a leading cause of mortality worldwide, with higher risks to develop pulmonary infections, including Aspergillus infections. Mechanisms underlying increased susceptibility to infections are poorly understood. Chronic ethanol consumption induced increased mortality rates, higher Aspergillus fumigatus burden and reduced neutrophil recruitment into the airways. Intravital microscopy showed decrease in leukocyte adhesion and rolling after ethanol consumption. Moreover, downregulated neutrophil activation and increased levels of serum CXCL1 in ethanol-fed mice induced internalization of CXCR2 receptor in circulating neutrophils. Bone marrow-derived neutrophils from ethanol-fed mice showed lower fungal clearance and defective reactive oxygen species production. Taken together, results showed that ethanol affects activation, recruitment, phagocytosis and killing functions of neutrophils, causing susceptibility to pulmonary A. fumigatus infection. This study establishes a new paradigm in innate immune response in chronic ethanol consumers.
Highlights
Ethanol abuse is a leading cause of mortality worldwide (World Health Organisation, 2014)
We found no significant differences in the levels of neutrophil chemotactic mediator CXCL1 after A. fumigatus infection in bronchoalveolar lavage fluid (BALF) of ethanol-treated mice compared to control group (Figure 3A)
We demonstrate that almost all cells migrated to the airways represent neutrophils, one of the most important cells involved in killing and control of A. fumigatus infection (Erwig and Gow, 2016)
Summary
Ethanol abuse is a leading cause of mortality worldwide (World Health Organisation, 2014). Malacco et al discovered that after chronic alcohol consumption, neutrophils were less reactive to inflammatory signals and less likely to reach the lungs They were less effective in dealing with the infection. If conidia pass through the initial barrier, alveolar macrophage (AM) phagocytosis takes place, resulting in a cascade of cytokine and chemokine release to recruit neutrophils to prevent fungal development (Dagenais and Keller, 2009; Caffrey-Carr et al, 2017) In all these circumstances, an altered leukocyte function may be a major risk factor for IA. Ethanol consumption is responsible for an impaired neutrophil function characterized by less phagocytosis, killing, and oxidative burst leading to elevated lung pathology in mice and accentuated mortality rates after infection
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