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

Bethany J. Hsia, Julie G. Ledford, Erin N. Potts-Kant, Vinayak S. Nikam, Njira L. Lugogo, W. Michael Foster, Monica Kraft, Soman N. Abraham, Jo Rae Wright

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 -/-KitW-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-/-KitW-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.

Original languageEnglish (US)
Pages (from-to)205-214.e2
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jul 2012


  • Mast cells
  • Mycoplasma species
  • TNF
  • airway hyperresponsiveness
  • mucus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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