Surfactant Collectins and Innate Immunity

Abstract

Respiratory pathogens encounter various lines of defenses before infection of the host is established. The innate immune response represents an important first-line protection mechanism against potentially pathogenic microorganisms during early stages of infection of the naive host. Important players in this host defense system are ‘collectins’, a class of soluble innate immune proteins. Well-characterized members of the collectin family are the surfactant proteins A (SP-A) and D (SP-D). These collectins are expressed in the lung and also in extrapulmonary mucosal tissues. Collectins are secreted as multimers resulting in trimeric clustering of the lectin domains which enables recognition of evolutionary conserved sugar patterns present on the surface of a large variety of pathogens. Binding to collectins may lead to direct agglutination and neutralization of pathogens, to opsonization in order to present bound microbes directly to phagocytes, to modulation of the inflammatory response and to regulation of dendritic cell and T cell functions. In pulmonary tissue, this early acute-phase-like response can be regarded as a crucial layer of protection against a vast array of pathogens that escape the physical barriers and threaten to infect the delicate respiratory epithelium. An important clinical application may be the inhalation, or instillation of collectin-based drugs as part of surfactant therapy, to prevent and treat infectious and inflammatory diseases of newborn infants.

The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

“…The hydrophilic surfactant proteins present in native surfactant, SP-A and SP-D, are removed due to their role in the innate immune response [12]. It is important to consider that SP-A, which is the major protein component in native lung surfactant, can stimulate cellular binding and uptake in alveolar macrophages [33].…”

“…The lipid fraction consists mainly of phospholipids (about 80-85 wt%) and a minor portion of neutral lipids (~10-20 wt%). SP-A and SP-D are high molecular weight hydrophilic proteins, that play a role in the innate immune response [12]. In contrast, SP-B and SP-C are small hydrophobic proteins that facilitate formation and stabilization of the surfactant film [13].…”

Glycoprotein analysis of porcine bronchoalveolar lavage fluid reveals potential biomarkers corresponding to resistance toActinobacillus pleuropneumoniaeinfection

“…Thus, the protein alpha-1-acid glycoprotein has been reported to have anti-inflammatory and immunomodulatory functions that are exclusively mediated by its carbohydrate chains [14]. Furthermore, a number of respiratory pathogens are recognized and neutralized by members of the collectin protein family during the early stages of infection [16]. Expression of pulmonary surfactant protein D (SP-D) was shown as increased during acute and chronic Actinobacillus pleuropneumoniae infection.…”

Introduction of N-Linked Glycans in the Lectin Domain of Surfactant Protein D

“…neutrophils, macrophages) and soluble factors that can inhibit infection directly, but that also can enhance neutralization and clearance of microorganisms by interacting with host immune cells (2)(3)(4). An important class of mammalian innate immune proteins known as "collectins" is involved in this early immune response to limit infection and spread of pathogens at mucosal surfaces of the naive host (5,6). Well characterized members of these collagenous C-type lectins are the two lung collectins, surfactant proteins A (SP-A) and D (SP-D, reviewed in Ref.…”