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.

Immunity to gastrointestinal nematode infections

“…173 Increased mucus production and the mucin switch are largely driven by IL-13, 173 IL-4, 174 and IL-22, 175 but the principle of physical obstruction provided by mucus layers can also be extended to other mucosal sites such as the lungs where the lectin surfactant protein-D, which acts as a lubricant, is needed for optimal protection against the pulmonary stage of N. brasiliensis infection. 176 Another expulsion mechanism is the release of various proteins by activated granulocytes and epithelial cells, most of which are toxic to parasites. The relative contribution of each molecule is highly context dependent.…”

Non-Pulmonary Immune Functions of Surfactant Proteins A and D

“…In vivo experiments on the porcine GIT showed that SP-D aggregates a variety of Gram-negative bacteria, thereby enhancing the uptake of these pathogens by intestinal epithelial cells, allowing for a more rapid immune response [43] . SP-D may also contribute to the control of parasitic helminth infections based on observations that non-lung SP-D also contributes to the resolution of N. brasiliensis infection; however, we do not currently understand how this effect may be mediated [15] .…”

“…Additionally, it has recently been shown that pulmonary SP-D contributes significantly to host control of infections by the parasitic helminth Nippostrongylus brasiliensis [15] . Recognition and binding of this diverse variety of incoming pathogens by SP-A and SP-D trigger various immune responses, including opsonisation leading to enhanced phagocytosis and killing by recruited macrophages and neutrophils via oxidative mechanisms, aggregation of pathogens thereby hindering their entry into host cells, and direct microbicidal activities by increasing cellular membrane permeability (reviewed in [2] ).…”

The role of rare innate immune cells in Type 2 immune activation against parasitic helminths

“…While this study did not address where the interaction between ILC2s and T cells may occur – in the tissue site (LP) or in the dLN – the authors showed that ILC2s could drive the differentiation of Th2 cells without direct contact (Pelly et al , 2016). In addition, IL-13-producing ILC2s can also cooperate with CD4 + T cells during N. brasiliensis infection to induce larval killing following secondary infection (Bouchery et al , 2015) as the larvae transit through the lung before becoming resident in the small intestine (Camberis et al , 2003), and these IL-13 + ILC2s are dependent on epithelial cell production of Surfactant Protein D (Thawer et al , 2016). Notably, whether ILC2s can initiate priming of Th2 cells via direct contact with naïve T cells is somewhat contentious.…”