Surfactant Protein-D Is Essential for Immunity to Helminth Infection.

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

doi:10.1371/journal.ppat.1005461

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.

Highlights

Surfactant Protein (SP)-D is a constitutively expressed C-type lectin, which has a well recognized role in innate pulmonary immunity against viruses, bacteria and fungi, as well as in maintaining pulmonary homeostasis [1]
Since the lung is an important site for immunity to N. brasiliensis infection [18, 19], we examined if host immunity to N. brasiliensis infection increased pulmonary and systemic levels of Surfactant Protein D (SP-D)
Analysis of bronchoalveolar lavage (BAL) (Fig 1A) and serum (S1A Fig) of N. brasiliensis-infected mice showed a temporal relationship between SP-D levels and progression and resolution of N. brasiliensis infection

Summary

Introduction

Surfactant Protein (SP)-D is a constitutively expressed C-type lectin, which has a well recognized role in innate pulmonary immunity against viruses, bacteria and fungi, as well as in maintaining pulmonary homeostasis [1]. Direct SP-D interactions with immune (such as alveolar macrophages [2]) and non-immune cells [3] can protect against immune pathologies such as chronic obstructive pulmonary disorder (COPD): SP-D-deficient (SP-D-/-) mice develop spontaneous chronic lung inflammation and emphysema [4], which can be prevented by recombinant SP-D replacement [5]. SP-D binding of pathogens and allergens is important for preventing or reducing the onset of pathology following infections such as respiratory syncytial virus (RSV) and influenza, and protects against airway inflammation [6, 7]. SP-D is likely to play an important role in limiting overzealous type 2 responses and immune-associated pathology in the lung. SP-D can interact directly with myeloid cells to enhance antigen or pathogen clearance by macrophages, and to regulate potentially damaging macrophage-driven inflammatory responses [5, 11]

Methods

Results

Discussion

Conclusion