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Distal respiratory tract viral infections in young children trigger a marked increase in alveolar mast cells

Andersson, Cecilia K LU ; Shikhagaie, Medya LU ; Mori, Michiko LU ; Al-Garawi, Amal ; Reed, Jennifer L ; Humbles, Alison A ; Welliver, Robert ; Mauad, Thais ; Bjermer, Leif LU and Jordana, Manel , et al. (2018) In ERJ Open Research 4(4).
Abstract

Viral infections predispose to the development of childhood asthma, a disease associated with increased lung mast cells (MCs). This study investigated whether viral lower respiratory tract infections (LRTIs) can already evoke a MC response during childhood. Lung tissue from young children who died following LRTIs were processed for immunohistochemical identification of MCs. Children who died from nonrespiratory causes served as controls. MCs were examined in relation to sensitisation in infant mice exposed to allergen during influenza A infection. Increased numbers of MCs were observed in the alveolar parenchyma of children infected with LRTIs (median (range) 12.5 (0-78) MCs per mm2) compared to controls (0.63 (0-4) MCs per mm2,... (More)

Viral infections predispose to the development of childhood asthma, a disease associated with increased lung mast cells (MCs). This study investigated whether viral lower respiratory tract infections (LRTIs) can already evoke a MC response during childhood. Lung tissue from young children who died following LRTIs were processed for immunohistochemical identification of MCs. Children who died from nonrespiratory causes served as controls. MCs were examined in relation to sensitisation in infant mice exposed to allergen during influenza A infection. Increased numbers of MCs were observed in the alveolar parenchyma of children infected with LRTIs (median (range) 12.5 (0-78) MCs per mm2) compared to controls (0.63 (0-4) MCs per mm2, p=0.0005). The alveolar MC expansion was associated with a higher proportion of CD34+ tryptase+ progenitors (controls: 0% (0-1%); LRTIs: 0.9% (0-3%) CD34+ MCs (p=0.01)) and an increased expression of the vascular cell adhesion molecule (VCAM)-1 (controls: 0.2 (0.07-0.3); LRTIs: 0.3 (0.02-2) VCAM-1 per mm2 (p=0.04)). Similarly, infant mice infected with H1N1 alone or together with house dust mite (HDM) developed an increase in alveolar MCs (saline: 0.4 (0.3-0.5); HDM: 0.6 (0.4-0.9); H1N1: 1.4 (0.4-2.0); HDM+H1N1: 2.2 (1.2-4.4) MCs per mm2 (p<0.0001)). Alveolar MCs continued to increase and remained significantly higher into adulthood when exposed to H1N1+HDM (day 36: 2.2 (1.2-4.4); day 57: 4.6 (1.6-15) MCs per mm2 (p=0.01)) but not when infected with H1N1 alone. Our data demonstrate that distal viral infections in young children evoke a rapid accumulation of alveolar MCs. Apart from revealing a novel immune response to distal infections, our data may have important implications for the link between viral infections during early childhood and subsequent asthma development.

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publishing date
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Contribution to journal
publication status
published
subject
in
ERJ Open Research
volume
4
issue
4
publisher
European Respiratory Society
external identifiers
  • pmid:30480000
  • scopus:85079478242
ISSN
2312-0541
DOI
10.1183/23120541.00038-2018
language
English
LU publication?
yes
id
9300ef3a-bce0-451c-97b9-448656f271e5
date added to LUP
2019-06-25 10:03:54
date last changed
2024-04-16 14:17:40
@article{9300ef3a-bce0-451c-97b9-448656f271e5,
  abstract     = {{<p>Viral infections predispose to the development of childhood asthma, a disease associated with increased lung mast cells (MCs). This study investigated whether viral lower respiratory tract infections (LRTIs) can already evoke a MC response during childhood. Lung tissue from young children who died following LRTIs were processed for immunohistochemical identification of MCs. Children who died from nonrespiratory causes served as controls. MCs were examined in relation to sensitisation in infant mice exposed to allergen during influenza A infection. Increased numbers of MCs were observed in the alveolar parenchyma of children infected with LRTIs (median (range) 12.5 (0-78) MCs per mm2) compared to controls (0.63 (0-4) MCs per mm2, p=0.0005). The alveolar MC expansion was associated with a higher proportion of CD34+ tryptase+ progenitors (controls: 0% (0-1%); LRTIs: 0.9% (0-3%) CD34+ MCs (p=0.01)) and an increased expression of the vascular cell adhesion molecule (VCAM)-1 (controls: 0.2 (0.07-0.3); LRTIs: 0.3 (0.02-2) VCAM-1 per mm2 (p=0.04)). Similarly, infant mice infected with H1N1 alone or together with house dust mite (HDM) developed an increase in alveolar MCs (saline: 0.4 (0.3-0.5); HDM: 0.6 (0.4-0.9); H1N1: 1.4 (0.4-2.0); HDM+H1N1: 2.2 (1.2-4.4) MCs per mm2 (p&lt;0.0001)). Alveolar MCs continued to increase and remained significantly higher into adulthood when exposed to H1N1+HDM (day 36: 2.2 (1.2-4.4); day 57: 4.6 (1.6-15) MCs per mm2 (p=0.01)) but not when infected with H1N1 alone. Our data demonstrate that distal viral infections in young children evoke a rapid accumulation of alveolar MCs. Apart from revealing a novel immune response to distal infections, our data may have important implications for the link between viral infections during early childhood and subsequent asthma development.</p>}},
  author       = {{Andersson, Cecilia K and Shikhagaie, Medya and Mori, Michiko and Al-Garawi, Amal and Reed, Jennifer L and Humbles, Alison A and Welliver, Robert and Mauad, Thais and Bjermer, Leif and Jordana, Manel and Erjefält, Jonas S}},
  issn         = {{2312-0541}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{European Respiratory Society}},
  series       = {{ERJ Open Research}},
  title        = {{Distal respiratory tract viral infections in young children trigger a marked increase in alveolar mast cells}},
  url          = {{http://dx.doi.org/10.1183/23120541.00038-2018}},
  doi          = {{10.1183/23120541.00038-2018}},
  volume       = {{4}},
  year         = {{2018}},
}