Protective effects of surfactant protein D treatment in 1,3-β-glucan-modulated allergic inflammation

Abstract

Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-β-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan, or OVA/1,3-β-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-β-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd(-/-) mice, supporting previously reported protective effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-β-glucan, but were reversed with rfhSP-D treatment. 1,3-β-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in bronchoalveolar lavage, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-β-Glucan reduced OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-γ production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-β-glucan-mediated neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D protects from mold-induced exacerbations of allergic asthma.

Fungal Exposure and Asthma: IgE and Non-IgE-Mediated Mechanisms

“…More recently, the role of β-glucans has been directly examined. One study found that exposure to curdlan plus OVA allergen resulted in a modest increase in lung inflammation and neutrophilia in mice [73]. Recently, our group directly compared exposure to fungal spores combined with house dust mite (HDM) allergen and curdlan plus HDM in a mouse model of asthma [12••].…”

Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation

“…Although the model is different to our allergic model, it partly explains decreased IL-5 production and airway eosinophilia in SP-D deficiency. However, a previous study showed that the number of eosinophilia and the production of Th2 cytokines increased in SP-D-deficient mice compared with WT mice after OVA challenge (Schaub et al 2004), while another study showed no difference in eosinophilia between SP-D-deficient and WT mice (Fakih et al 2015). The different protocols of OVA sensitization/challenge may be associated with the different results among these studies.…”

“…), while another study showed no difference in eosinophilia between SP‐D‐deficient and WT mice (Fakih et al. ). The different protocols of OVA sensitization/challenge may be associated with the different results among these studies.…”

Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D

“…This could indicate that OVA-sensitization and challenge that induce inflammation also reduces variation in microbiota composition. It is worth noting that there were only mild allergic differences between OVA-sensitized and challenged Sftpd+/+ and S ftpd−/-, [21] making it possible to separate the effects of SP-D and allergy on the gut microbiota.…”