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 receptors 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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Nathalia Luisa Sousa de Oliveira Malacco

    Genetics, Ecology and Evolution, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    For correspondence
    nathalialuisa2@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
  2. Jessica Amanda Marques Souza

    Genetics, Ecology and Evolution, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  3. Flavia Rayssa Braga Martins

    Genetics, Ecology and Evolution, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Milene Alvarenga Rachid

    Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  5. Janaina Aparecida Simplicio

    Psychiatric Nursing and Human Sciences, Universidade de São Paulo, Ribeirão Preto, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  6. Carlos Renato Tirapelli

    Psychiatric Nursing and Human Sciences, Universidade de São Paulo, Ribeirão Preto, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  7. Adriano de Paula Sabino

    Clinical and Toxicological Analysis, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  8. Celso Martins Queiroz-Junior

    Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  9. Grazielle Ribeiro Goes

    Biology, Universidade do Estado de Minas Gerais, Divinópolis, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  10. Leda Quercia Vieira

    Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  11. Danielle Glória Souza

    Microbiology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  12. Vanessa Pinho

    Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  13. Mauro Martins Teixeira

    Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  14. Frederico Marianetti Soriani

    Genetics, Ecology and Evolution, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    For correspondence
    fredsori@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4720-6746

Funding

Fundação de Amparo à Pesquisa do Estado de Minas Gerais (APQ-01756-10,APQ-02198-14 and APQ-03950-17;)

  • Jessica Amanda Marques Souza
  • Leda Quercia Vieira
  • Danielle Glória Souza
  • Vanessa Pinho
  • Mauro Martins Teixeira
  • Frederico Marianetti Soriani

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (001)

  • Nathalia Luisa Sousa de Oliveira Malacco
  • Jessica Amanda Marques Souza

Conselho Nacional de Desenvolvimento Científico e Tecnológico (474528-2012- 0 and 483184-2011-0)

  • Frederico Marianetti Soriani

Instituto Nacional de Ciência e Tecnologia em Dengue e Interações Microrganismo-Hospedeiro

  • Nathalia Luisa Sousa de Oliveira Malacco
  • Jessica Amanda Marques Souza
  • Flavia Rayssa Braga Martins
  • Leda Quercia Vieira
  • Danielle Glória Souza
  • Vanessa Pinho
  • Mauro Martins Teixeira
  • Frederico Marianetti Soriani

Universidade Federal de Minas Gerais (001)

  • Nathalia Luisa Sousa de Oliveira Malacco
  • Jessica Amanda Marques Souza
  • Flavia Rayssa Braga Martins
  • Milene Alvarenga Rachid
  • Celso Martins Queiroz-Junior
  • Grazielle Ribeiro Goes
  • Leda Quercia Vieira
  • Danielle Glória Souza
  • Vanessa Pinho
  • Mauro Martins Teixeira
  • Frederico Marianetti Soriani

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations of the CONCEA (Conselho Nacional de Controle de Experimentação Animal) from Brazil. All animal experiments received prior approval from the Animal Ethics Committee (CEUA) of Universidade Federal de Minas Gerais (UFMG), Brazil (Protocol number: 4/2015).

Copyright

© 2020, Malacco et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 7,096
    views
  • 270
    downloads
  • 14
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Nathalia Luisa Sousa de Oliveira Malacco
  2. Jessica Amanda Marques Souza
  3. Flavia Rayssa Braga Martins
  4. Milene Alvarenga Rachid
  5. Janaina Aparecida Simplicio
  6. Carlos Renato Tirapelli
  7. Adriano de Paula Sabino
  8. Celso Martins Queiroz-Junior
  9. Grazielle Ribeiro Goes
  10. Leda Quercia Vieira
  11. Danielle Glória Souza
  12. Vanessa Pinho
  13. Mauro Martins Teixeira
  14. Frederico Marianetti Soriani
(2020)
Chronic ethanol consumption compromises neutrophil function in acute pulmonary Aspergillus fumigatus infection
eLife 9:e58855.
https://doi.org/10.7554/eLife.58855

Share this article

https://doi.org/10.7554/eLife.58855

Further reading

    1. Computational and Systems Biology
    2. Immunology and Inflammation
    Peng Li, Sree Pulugulla ... Warren J Leonard
    Short Report

    Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partners and DNA motif spacing preferences. Using SPICE, we successfully identified known composite elements, such as AP1-IRF composite elements (AICEs) and STAT5 tetramers, and also uncovered several novel binding partners, including JUN-IKZF1 composite elements. One such novel interaction was identified at CNS9, an upstream conserved noncoding region in the human IL10 gene, which harbors a non-canonical IKZF1 binding site. We confirmed the cooperative binding of JUN and IKZF1 and showed that the activity of an IL10-luciferase reporter construct in primary B and T cells depended on both this site and the AP1 binding site within this composite element. Overall, our findings reveal an unappreciated global association of IKZF1 and AP1 and establish SPICE as a valuable new pipeline for predicting novel transcription binding complexes.

    1. Immunology and Inflammation
    2. Medicine
    Edwin A Homan, Ankit Gilani ... James C Lo
    Short Report

    Together with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood. In human and mouse, C3AR1 in the liver is expressed primarily in Kupffer cells, but is downregulated in humans with MASLD compared to obese controls. To test the role of complement 3a receptor (C3aR1) on macrophages and liver resident macrophages in MASLD, we generated mice deficient in C3aR1 on all macrophages (C3aR1-MφKO) or specifically in liver Kupffer cells (C3aR1-KpKO) and subjected them to a model of metabolic steatotic liver disease. We show that macrophages account for the vast majority of C3ar1 expression in the liver. Overall, C3aR1-MφKO and C3aR1-KpKO mice have similar body weight gain without significant alterations in glucose homeostasis, hepatic steatosis and fibrosis, compared to controls on a MASLD-inducing diet. This study demonstrates that C3aR1 deletion in macrophages or Kupffer cells, the predominant liver cell type expressing C3ar1, has no significant effect on liver steatosis, inflammation or fibrosis in a dietary MASLD model.