Surfactant protein-D is essential for immunity to helminth infection

Sumaiyya Thawer, Jennifer Auret, Corinna Schnoeller, Alisha Chetty, Katherine Smith, Matthew Darby, Luke Roberts, Rosie-Marie Mackay, Harry J Whitwell, John F Timms, Jens Madsen, Murray E Selkirk, Frank Brombacher, Howard William Clark, William G C Horsnell

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)
101 Downloads (Pure)

Abstract

Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2), elevated expression of markers of alternative activation by alveolar macrophages (alvM) and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naïve recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD) to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths.

Original languageEnglish
Article numbere1005461
Number of pages18
JournalPLoS pathogens
Volume12
Issue number2
DOIs
Publication statusPublished - 22 Feb 2016

Keywords

  • Animals
  • Epithelial Cells
  • Immunity, Innate
  • Interleukin-13
  • Interleukin-4
  • Lung
  • Macrophages, Alveolar
  • Mice
  • Nippostrongylus
  • Pulmonary Surfactant-Associated Protein D
  • Strongylida Infections
  • Journal Article
  • Research Support, Non-U.S. Gov't

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