Influenza suppresses neutrophil recruitment to the lung and exacerbates secondary invasive pulmonary aspergillosis
| Autor: | Kara L Nickolich, Joshua M. Tobin, Matthew J Pilewski, John F. Alcorn, Krishnaveni Ramanan, Kristina D Lamens, Keven M. Robinson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Neutrophils Chemokine CXCL1 Immunology Colony Count Microbial Article Aspergillus fumigatus 03 medical and health sciences Mice 0302 clinical medicine Influenza A Virus H1N1 Subtype Orthomyxoviridae Infections Influenza Human medicine Immunology and Allergy Animals Humans Lung Immune Evasion Invasive Pulmonary Aspergillosis Mice Knockout biology business.industry Respiratory disease respiratory system medicine.disease biology.organism_classification Neutrophilia CXCL1 Mice Inbred C57BL medicine.anatomical_structure STAT1 Transcription Factor Neutrophil Infiltration Disease Progression Respiratory virus medicine.symptom business Viral load 030215 immunology Respiratory tract Signal Transduction |
| Zdroj: | J Immunol |
| Popis: | Aspergillus fumigatus is an environmental fungus that can cause invasive pulmonary aspergillosis when spores are inhaled into the respiratory tract and invade airway or lung tissue. Influenza is a common respiratory virus that can cause severe respiratory disease, and postinfluenza invasive pulmonary aspergillosis, which is becoming a well-recognized clinical problem, typically occurs in critically ill patients. Mice challenged with influenza A PR/8/34 H1N1 and subsequently challenged with A. fumigatus had increased fungal burden, viral burden, inflammation, and mortality compared with single infected mice. Neutrophil recruitment in the lung of superinfected mice was decreased; however, mice were not neutropenic, and there was no difference in absolute blood neutrophils between groups. Additionally, CXCL1 and CXCL2 were decreased in lungs of superinfected mice compared with controls. IFN levels were increased in mice that received influenza, and deletion of STAT1 resulted in decreased fungal burden, increased airway and lung neutrophils, and increased CXCL1 compared with wild-type mice, whereas deletion of STAT2 did not change fungal burden or airway neutrophilia compared with wild-type mice. These data demonstrate a mechanism by which influenza A–induced STAT1 signaling inhibits neutrophil recruitment and increases susceptibility to postinfluenza invasive pulmonary aspergillosis. |
| Databáze: | OpenAIRE |
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