Surfactant Protein-D is essential for immunity to helminth infection

Thawer, Sumaiyya, Auret, Jennifer, Schnoeller, Corinna, Chetty, Alisha, Smith, Katherine A. ORCID: https://orcid.org/0000-0001-8150-5702, Darby, Matthew, Roberts, Luke, Mackay, Rosie-Marie, Whitwell, Harry J., Timms, John F., Madsen, Jens, Selkirk, Murray E., Brombacher, Frank, Clark, Howard William and Horsnell, William G. C. 2016. Surfactant Protein-D is essential for immunity to helminth infection. PLoS Pathogens 12 (2) , e1005461. 10.1371/journal.ppat.1005461

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General)
Publisher:	Public Library of Science
ISSN:	1553-7374
Date of First Compliant Deposit:	24 May 2016
Date of Acceptance:	28 January 2016
Last Modified:	06 May 2023 07:54
URI:	https://orca.cardiff.ac.uk/id/eprint/91201

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