Surfactant Proteins in Pulmonary Immunity and Host Defense

Pulmonary surfactant proteins are specialised molecules that reduce surface tension in the alveoli and serve as pivotal mediators of lung host defence. Four principal proteins—SP-A, SP-B, SP-C and SP-D—are secreted by type II alveolar cells into the air–liquid interface. Beyond biophysical roles in maintaining alveolar stability, SP-A and SP-D function as soluble pattern recognition receptors that bind pathogens, agglutinate microbes and enhance phagocytosis by alveolar macrophages. SP-B and SP-C, though primarily structural, contribute to antimicrobial barrier function by stabilising surfactant organisation and influencing immune cell interactions. These proteins modulate inflammatory responses to bacteria, viruses and allergens, facilitate resolution of inflammation and bridge innate and adaptive immunity through effects on dendritic cell maturation and lymphocyte activation. Dysregulation or deficiency of surfactant proteins has been implicated in acute lung injury, chronic airway disease, fibrosis and susceptibility to infection. Recombinant forms and targeted modulation of surfactant components are under investigation as diagnostics, prognostic biomarkers and novel therapeutics to restore pulmonary homeostasis and host defence.

Research from Nature Portfolio

Recent studies have demonstrated that SP-D directly modulates mucin secretion by airway epithelial cells through engagement of signal regulatory protein α (SIRPα) and activation of SH2 domain-containing tyrosine phosphatase-1, resulting in dephosphorylation of extracellular signal-regulated kinase and attenuation of MUC5AC overproduction. In vitro air–liquid interface cultures of human bronchial epithelial cells exposed to benzo(a)pyrene exhibited pronounced mucin induction, which was significantly suppressed by SP-D treatment. Complementary in vivo experiments confirmed that intratracheal administration of SP-D reduced pollutant-induced ERK phosphorylation and goblet cell hyperplasia in murine airways. These findings reveal a direct epithelial mechanism for surfactant-mediated protection against mucin hypersecretion, offering potential therapeutic pathways for chronic obstructive pulmonary disease and asthma management.

Surfactant Proteins in Pulmonary Immunity and Host Defense publication trend

The graph below shows the total number of articles in surfactant proteins in pulmonary immunity and host defense across all publications each year (not limited to Nature Index journals).

Technical terms

Collectin: A family of collagen-containing C-type lectins that bind carbohydrate patterns on pathogens to promote aggregation and clearance.

Carbohydrate recognition domain (CRD): The lectin domain of collectins responsible for recognising sugar moieties on microbial surfaces.

Pathogen-associated molecular pattern (PAMP): Distinct molecular signatures on microbes recognised by innate immune receptors.

Signal regulatory protein α (SIRPα): A transmembrane receptor on epithelial and immune cells that mediates inhibitory signalling upon ligand binding.

Mucin 5AC (MUC5AC): A gel-forming mucin secreted by goblet cells, commonly upregulated in chronic airway diseases.

References

1. Revisiting surfactant protein D: an immune surveillance molecule bridging innate and adaptive immunity. Frontiers in Immunology (2024).
2. Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα. Scientific Reports (2024).
3. Circulating Surfactant Protein D: A Biomarker for Acute Lung Injury?. Biomedicines (2023).
4. SP-A and SP-D: Dual Functioning Immune Molecules With Antiviral and Immunomodulatory Properties. Frontiers in Immunology (2021).