Chronic ethanol consumption compromises neutrophil function in acute pulmonary Aspergillus fumigatus infection

Elife. 2020 Jul 23;9:e58855. doi: 10.7554/eLife.58855.

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.

Keywords: acute lung infection; aspergillosis; chronic ethanol consumption; ethanol consumption; immunology; infectious disease; inflammation; microbiology; mouse; neutrophil; neutrophil recruitment.

Plain Language Summary

Alcoholism is a chronic disease that has many damaging effects on the body. Over long periods, excessive alcohol intake weakens the immune system, putting consumers at increased risk of getting lung infections such as pneumonia. Some forms of pneumonia can be caused by the fungus Aspergillus fumigatus. This microbe does not tend to be a problem for healthy individuals, but it can be fatal for those with impaired immune systems. Here, Malacco et al. wanted to find out why excessive alcohol consumers are more prone to pneumonia. To test this, the researchers used two groups of mice that were either fed plain water or water containing ethanol. After 12 weeks, both groups were infected with Aspergillus fumigatus. The results showed that alcohol-fed mice were more susceptible to the infection caused by strong inflammation of the lungs. Normally, the immune system confronts a lung infection by activating a group of defense cells called neutrophils, which travel through the blood system to the infection site. Once in the right spot, neutrophils get to work by releasing toxins that kill the fungus. 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 also less effective in dealing with the infection. Neutrophil released fewer toxins and were thus less able to kill the microbial cells. These findings demonstrate for the first time how alcohol can affect immune cells during infection and pave the way for new possibilities to prevent fatal lung infections in excessive alcohol consumers. A next step would be to identify how alcohol acts on other processes in the body and to find a way to modulate or even revert the changes it causes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Aspergillosis / chemically induced
  • Aspergillosis / immunology*
  • Aspergillosis / pathology
  • Aspergillus fumigatus / immunology*
  • CD11b Antigen / metabolism
  • Chemotaxis / drug effects
  • Cytokines / immunology
  • Disease Susceptibility
  • Ethanol / adverse effects*
  • Inflammation / chemically induced
  • L-Selectin / metabolism
  • Lung Diseases, Fungal / chemically induced
  • Lung Diseases, Fungal / immunology*
  • Lung Diseases, Fungal / microbiology
  • Lung Diseases, Fungal / pathology
  • Lymphocytes / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Phagocytosis / drug effects
  • Receptors, Interleukin-8B / metabolism
  • Respiratory Burst / drug effects

Substances

  • CD11b Antigen
  • Cxcr2 protein, mouse
  • Cytokines
  • Itgam protein, mouse
  • Receptors, Interleukin-8B
  • L-Selectin
  • Ethanol