Surfactant Protein-D Is Essential for Immunity to Helminth Infection.
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Author(s)
Type
Journal Article
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.
Date Issued
2016-02-22
Date Acceptance
2016-01-28
Citation
PLOS Pathogens, 2016, 12 (2)
ISSN
1553-7366
Publisher
Public Library of Science
Journal / Book Title
PLOS Pathogens
Volume
12
Issue
2
Copyright Statement
© 2016 Thawer et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
License URL
Sponsor
Wellcome Trust
Identifier
PII: PPATHOGENS-D-15-02038
Grant Number
097011/Z/11/Z
Subjects
Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
e1005461