title: Surfactant Protein-D Is Essential for Immunity to Helminth Infection.
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.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology and Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: Sumaiyya
authors.initials: S
authors.lastname: Thawer
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology and Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Auret
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Corinna
authors.initials: C
authors.lastname: Schnoeller
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology and Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: Alisha
authors.initials: A
authors.lastname: Chetty
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology and Division of Immunology, University of Cape Town, Cape Town, South Africa.|Institute of Infection and Immunity, University of Cardiff, Cardiff, United Kingdom.
authors.forename: Katherine
authors.initials: K
authors.lastname: Smith
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology and Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: Matthew
authors.initials: M
authors.lastname: Darby
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Roberts
authors.affiliation: Clinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom.
authors.forename: Rosie-Marie
authors.initials: RM
authors.lastname: Mackay
authors.affiliation: Cancer Proteomics, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Whitwell
authors.affiliation: Cancer Proteomics, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: John F
authors.initials: JF
authors.lastname: Timms
authors.affiliation: Clinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom.
authors.forename: Jens
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Murray E
authors.initials: ME
authors.lastname: Selkirk
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology and Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.affiliation: Clinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom.
authors.forename: Howard William
authors.initials: HW
authors.lastname: Clark
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology and Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: William G C
authors.initials: WG
authors.lastname: Horsnell
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000276:immunology / Q000469:parasitology*; D007113:Immunity, Innate / Q000276:immunology; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000469:parasitology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D009559:Nippostrongylus / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000378:metabolism*; D017206:Strongylida Infections / Q000276:immunology / Q000469:parasitology*
chemical_list: D018793:Interleukin-13; D037663:Pulmonary Surfactant-Associated Protein D; D015847:Interleukin-4