Mast cell TNF receptors regulate responses to Mycoplasma pneumoniae in surfactant protein A (SP-A)-/- mice.

Journal Article (Journal Article)

BACKGROUND: Mycoplasma pneumoniae (Mp) frequently colonizes the airways of patients with chronic asthma and likely contributes to asthma exacerbations. We previously reported that mice lacking surfactant protein A (SP-A) have increased airway hyperresponsiveness (AHR) during M pneumoniae infection versus wild-type mice mediated by TNF-α. Mast cells (MCs) have been implicated in AHR in asthma models and produce and respond to TNF-α. OBJECTIVE: Determine the contribution of MC/TNF interactions to AHR in airways lacking functional SP-A during Mp infection. METHODS: Bronchoalveolar lavage fluid was collected from healthy and asthmatic subjects to examine TNF-α levels and M pneumoniae positivity. To determine how SP-A interactions with MCs regulate airway homeostasis, we generated mice lacking both SP-A and MCs (SP-A(-/-)Kit(W-sh/W-sh)) and infected them with M pneumoniae. RESULTS: Our findings indicate that high TNF-α levels correlate with M pneumoniae positivity in human asthmatic patients and that human SP-A inhibits M pneumoniae-stimulated transcription and release of TNF-α by MCs, implicating a protective role for SP-A. MC numbers increase in M pneumoniae-infected lungs, and airway reactivity is dramatically attenuated when MCs are absent. Using SP-A(-/-)Kit(W-sh/W-sh) mice engrafted with TNF-α(-/-) or TNF receptor (TNF-R)(-/-) MCs, we found that TNF-α activation of MCs through the TNF-R, but not MC-derived TNF-α, leads to augmented AHR during M pneumoniae infection when SP-A is absent. Additionally, M pneumoniae-infected SP-A(-/-)Kit(W-sh/W-sh) mice engrafted with TNF-α(-/-) or TNF-R(-/-) MCs have decreased mucus production compared with that seen in mice engrafted with wild-type MCs, whereas burden was unaffected. CONCLUSION: Our data highlight a previously unappreciated but vital role for MCs as secondary responders to TNF-α during the host response to pathogen infection.

Full Text

Duke Authors

Cited Authors

  • Hsia, BJ; Ledford, JG; Potts-Kant, EN; Nikam, VS; Lugogo, NL; Foster, WM; Kraft, M; Abraham, SN; Wright, JR

Published Date

  • July 2012

Published In

Volume / Issue

  • 130 / 1

Start / End Page

  • 205 - 14.e2

PubMed ID

  • 22502799

Pubmed Central ID

  • PMC3578696

Electronic International Standard Serial Number (EISSN)

  • 1097-6825

Digital Object Identifier (DOI)

  • 10.1016/j.jaci.2012.03.002


  • eng

Conference Location

  • United States