Surfactant Protein-D Is Essential for Immunity to Helminth Infection

PLoS Pathog. 2016 Feb 22;12(2):e1005461. doi: 10.1371/journal.ppat.1005461. eCollection 2016 Feb.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epithelial Cells / immunology
  • Epithelial Cells / parasitology*
  • Immunity, Innate / immunology
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Lung / immunology
  • Lung / parasitology*
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / parasitology*
  • Mice
  • Nippostrongylus / immunology*
  • Pulmonary Surfactant-Associated Protein D / deficiency
  • Pulmonary Surfactant-Associated Protein D / metabolism*
  • Strongylida Infections / immunology
  • Strongylida Infections / parasitology*

Substances

  • Interleukin-13
  • Pulmonary Surfactant-Associated Protein D
  • Interleukin-4