Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essent...

Full description

Bibliographic Details
Main Authors: Qingyu Wu, Ilka Jorde, Olivia Kershaw, Andreas Jeron, Dunja Bruder, Jens Schreiber, Sabine Stegemann-Koniszewski
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/8/12/1878
_version_ 1797546547156615168
author Qingyu Wu
Ilka Jorde
Olivia Kershaw
Andreas Jeron
Dunja Bruder
Jens Schreiber
Sabine Stegemann-Koniszewski
author_facet Qingyu Wu
Ilka Jorde
Olivia Kershaw
Andreas Jeron
Dunja Bruder
Jens Schreiber
Sabine Stegemann-Koniszewski
author_sort Qingyu Wu
collection DOAJ
description Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI. Mice infected with a sublethal dose of IAV were sensitized and challenged in an ovalbumin mediated mouse model for AAI after resolution of the acute viral infection. Histological changes, respiratory leukocytes, cytokines and airway hyperreactivity were analyzed in resolved IAV infection alone and in AAI with and without previous IAV infection. More than five weeks after infection, we detected persistent pneumonia with increased activated CD4<sup>+</sup> and CD8<sup>+</sup> lymphocytes as well as dendritic cells and MHCII expressing macrophages in the lung. Resolved IAV infection significantly affected subsequently induced AAI on different levels including morphological changes, respiratory leukocytes and lymphocytes as well as the pro-inflammatory cytokine responses, which was clearly diminished. We conclude that IAV has exceptional persisting effects on respiratory immunity with substantial consequences for subsequently induced AAI.
first_indexed 2024-03-10T14:31:21Z
format Article
id doaj.art-b14fe7af8eb44d4da58c0c3796cf7086
institution Directory Open Access Journal
issn 2076-2607
language English
last_indexed 2024-03-10T14:31:21Z
publishDate 2020-11-01
publisher MDPI AG
record_format Article
series Microorganisms
spelling doaj.art-b14fe7af8eb44d4da58c0c3796cf70862023-11-20T22:34:10ZengMDPI AGMicroorganisms2076-26072020-11-01812187810.3390/microorganisms8121878Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse ModelQingyu Wu0Ilka Jorde1Olivia Kershaw2Andreas Jeron3Dunja Bruder4Jens Schreiber5Sabine Stegemann-Koniszewski6Experimental Pneumology, Department of Pneumology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Pneumology, Department of Pneumology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyInstitute of Veterinary Pathology, Department of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, GermanyInfection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyInfection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Pneumology, Department of Pneumology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Pneumology, Department of Pneumology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyAllergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI. Mice infected with a sublethal dose of IAV were sensitized and challenged in an ovalbumin mediated mouse model for AAI after resolution of the acute viral infection. Histological changes, respiratory leukocytes, cytokines and airway hyperreactivity were analyzed in resolved IAV infection alone and in AAI with and without previous IAV infection. More than five weeks after infection, we detected persistent pneumonia with increased activated CD4<sup>+</sup> and CD8<sup>+</sup> lymphocytes as well as dendritic cells and MHCII expressing macrophages in the lung. Resolved IAV infection significantly affected subsequently induced AAI on different levels including morphological changes, respiratory leukocytes and lymphocytes as well as the pro-inflammatory cytokine responses, which was clearly diminished. We conclude that IAV has exceptional persisting effects on respiratory immunity with substantial consequences for subsequently induced AAI.https://www.mdpi.com/2076-2607/8/12/1878influenza A virusallergic asthmaallergic airway inflammationrespiratory immune regulationpro-inflammatory cytokinesmacrophages
spellingShingle Qingyu Wu
Ilka Jorde
Olivia Kershaw
Andreas Jeron
Dunja Bruder
Jens Schreiber
Sabine Stegemann-Koniszewski
Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model
Microorganisms
influenza A virus
allergic asthma
allergic airway inflammation
respiratory immune regulation
pro-inflammatory cytokines
macrophages
title Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model
title_full Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model
title_fullStr Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model
title_full_unstemmed Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model
title_short Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model
title_sort resolved influenza a virus infection has extended effects on lung homeostasis and attenuates allergic airway inflammation in a mouse model
topic influenza A virus
allergic asthma
allergic airway inflammation
respiratory immune regulation
pro-inflammatory cytokines
macrophages
url https://www.mdpi.com/2076-2607/8/12/1878
work_keys_str_mv AT qingyuwu resolvedinfluenzaavirusinfectionhasextendedeffectsonlunghomeostasisandattenuatesallergicairwayinflammationinamousemodel
AT ilkajorde resolvedinfluenzaavirusinfectionhasextendedeffectsonlunghomeostasisandattenuatesallergicairwayinflammationinamousemodel
AT oliviakershaw resolvedinfluenzaavirusinfectionhasextendedeffectsonlunghomeostasisandattenuatesallergicairwayinflammationinamousemodel
AT andreasjeron resolvedinfluenzaavirusinfectionhasextendedeffectsonlunghomeostasisandattenuatesallergicairwayinflammationinamousemodel
AT dunjabruder resolvedinfluenzaavirusinfectionhasextendedeffectsonlunghomeostasisandattenuatesallergicairwayinflammationinamousemodel
AT jensschreiber resolvedinfluenzaavirusinfectionhasextendedeffectsonlunghomeostasisandattenuatesallergicairwayinflammationinamousemodel
AT sabinestegemannkoniszewski resolvedinfluenzaavirusinfectionhasextendedeffectsonlunghomeostasisandattenuatesallergicairwayinflammationinamousemodel