Pandemic influenza virus, pH1N1, induces asthmatic symptoms via activation of innate lymphoid cells.
BACKGROUND
The pandemic strain of the influenza A virus (pH1N1) in 2009 caused many complications in patients. In this study, we introduce asthmatic symptoms as a complication of pH1N1 infection in children, not having a relationship with asthma history. The aim of this study was to quantify asthmatic symptoms in pH1N1-infected children and elucidate the underlying mechanisms of airway hyper-responsiveness (AHR) induced in a murine model of pH1N1 infection.


METHODS
As a retrospective study, pH1N1-infected children who were hospitalized with moderate to severe acute asthmatic symptoms were enrolled and administered a methacholine challenge test (MCT) at 3 months post-discharge. Additionally, the induction of AHR by pH1N1 infection was measured by MCT in wild-type and Rag1(-/-) mice. The effect of the innate immune response on the development of AHR following pH1N1 infection was investigated.


RESULTS
More than 70% of the pH1N1-infected children without a pre-infection diagnosis of asthma had a negative response on the MCT. None of these children had recurrent wheezing or asthma during the 3 years following pH1N1 infection. The development of AHR in pH1N1-infected mice was associated with an elevation in IL-33 and innate lymphoid cells 2 (ILC2).


CONCLUSIONS
This study demonstrates that pH1N1 infection directly induces transient asthmatic symptoms in patients regardless of their medical history. pH1N1 infection was shown to stimulate the rapid development of AHR and Th2-type cytokine secretion in mice via the activation of ILC2; it may be activated independently of adaptive immunity.
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.|Departments of Food and Animal Biotechnology, School of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul, Republic of Korea.
D H
DH
Shim
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.|Department of Pediatrics and Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Y A
YA
Park
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.|Department of Pediatrics and Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
M J
MJ
Kim
Department of Pediatrics and Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Y
JY
Hong
Department of Pediatrics and Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Y
JY
Baek
Department of Pediatrics and Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
K W
KW
Kim
Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Y-H
YH
Byun
Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
B-L
BL
Seong
Departments of Food and Animal Biotechnology, School of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul, Republic of Korea.
S
S
Ryu
Laboratory Science Division, International Vaccine Institute, Seoul, Republic of Korea.
M K
MK
Song
ATgen Co. Ltd., Sungnam, 463-400, Republic of Korea.
K-J
KJ
Hong
Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.|University of Science and Technology, Daejeon, Republic of Korea.
W
W
Na
Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.|University of Science and Technology, Daejeon, Republic of Korea.
D
D
Song
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.
J H
JH
Park
Department of Pediatrics and Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
M H
MH
Sohn
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
J M
JM
Lee
D000293:Adolescent; D000818:Animals; D001249:Asthma / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D058873:Pandemics; D012189:Retrospective Studies
airway hyper-responsiveness; asthmatic symptoms; infection; influenza; innate lymphoid cells