Purpose
Transport 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).
Methods
Pigr 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 RT-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.
Results
Respiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impact respiratory Pigr expression and sIgA in URT vs . LRT, only prophylactic IFN-γ treatment reduces nasal colonization with S. pneumoniae .
Conclusion
Airway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment significantly improves antibacterial immunity in the URT.