Chronic ethanol consumption compromises neutrophil function in acute pulmonary Aspergillus fumigatus infection
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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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.
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