Chronic ethanol consumption compromises neutrophil function in acute pulmonary Aspergillus fumigatus infection
Nathália Luísa Sousa de Oliveira Malacco, Jéssica Amanda Marques Souza, Flávia Rayssa Braga Martins, Milene Alvarenga Rachid, Janaina A. Simplicio, Carlos R. Tirapelli, Adriano de Paula Sabino, Celso Martins Queiroz‐Junior, Grazielle Ribeiro Goes, Leda Quércia Vieira, Danielle G. Souza, Vanessa Pinho, Mauro Martins Teixeira, Frederico Marianetti Soriani
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.