Abstract
PurposeTransport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion.Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT).MethodsPigr gene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-γ-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-γ-treated mice were colonized with Streptococcus pneumoniae and bacterial CFUs were determined in URT and LRT.ResultsRespiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impacts respiratory Pigr expression and IgA in URT vs. LRT, only prophylactic IFN-γ treatment reduces nasal colonization with S. pneumoniae.ConclusionAirway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR.
Highlights
Airway epithelial cells (AECs) constitute the first line of defense against respiratory pathogens
In contrast to the unaltered or even reduced (NALT) Pigr expression levels in mice with an undefined microbiome, we detected significantly increased IgA concentration in the lower respiratory tract (LRT) (Fig. 2b) and URT (Fig. 2c) in this group, which was associated with a systemic IgA increase (Fig. 2d)
We observed that BALB/c as well as C57BL/6 J mice showed highest Pigr expression in trachea, followed by nasal-associated lymphoid tissue (NALT) and lung
Summary
Airway epithelial cells (AECs) constitute the first line of defense against respiratory pathogens. They express transmembrane proteins, which form tight junctions that allow only small ions or water to traverse paracellularly [1]. AECs constitutively secrete antimicrobial proteins, complement factors and cytokines, and rapidly mount antimicrobial immune responses upon inflammatory and infectious stimuli [5,6,7,8,9]. AECs have a central function in antibodymediated mucosal immunity. Multimeric IgA and IgM are actively transported through AECs via the polymeric immunoglobulin receptor (PIGR) and are secreted into the mucosal lumen as secretory immunoglobulins (SIgs) [10]. SIgA plays a crucial role in the regulation of Streptococcus pneumoniae nasal colonization in mice [12]
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