scholarly journals Exogenous and Endogenous Triggers Differentially Stimulate Pigr Expression and Antibacterial Secretory Immunity in the Murine Respiratory Tract

Lung ◽  
2021 ◽  
Author(s):  
Alexander Pausder ◽  
Jennifer Fricke ◽  
Klaus Schughart ◽  
Jens Schreiber ◽  
Till Strowig ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Immunoglobulin A ◽  
Airway Epithelial ◽  
Immunoglobulin Receptor ◽  
Therapeutic Implications ◽  
Secretory Immunity ◽  
Specific Pathogen ◽  
Ifn Γ ◽  
Immune Exclusion ◽  
Secretory Immunoglobulin

Abstract 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 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 impacts respiratory Pigr expression and IgA 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 modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR.

scholarly journals Exogenous and endogenous triggers differentially stimulate Pigr expression and antibacterial secretory immunity in the murine respiratory tract

2021 ◽  
Author(s):  
Alexander Pausder ◽  
Jennifer Fricke ◽  
Klaus Schughart ◽  
Jens Schreiber ◽  
Till Strowig ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Immunoglobulin A ◽  
Airway Epithelial ◽  
Immunoglobulin Receptor ◽  
Therapeutic Implications ◽  
Secretory Immunity ◽  
Specific Pathogen ◽  
Ifn Γ ◽  
Immune Exclusion ◽  
Secretory Immunoglobulin

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 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. 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 impact respiratory Pigr expression and sIgA 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 significantly improves antibacterial immunity in the URT.

scholarly journals Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin

2020 ◽  
Author(s):  
Yuxin Wang ◽  
Guopeng Wang ◽  
Yaxin Li ◽  
Hao Shen ◽  
Huarui Chu ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Immunoglobulin A ◽  
Underlying Mechanism ◽  
Secretory Component ◽  
Secretory Immunoglobulin A ◽  
Immunoglobulin Receptor ◽  
J Chain ◽  
Cryo Electron Microscopy ◽  
Structural Insights ◽  
Secretory Immunoglobulin

AbstractSecretory Immunoglobulin A (SIgA) is the most abundant antibody at the mucosal surface. SIgA possesses two additional subunits besides IgA: the joining chain (J-chain) and secretory component (SC). SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport IgA to the mucosa. The underlying mechanism of how the J-chain and pIgR/SC facilitates the assembly and secretion of SIgA remains to be understood. During the infection of Streptococcus pneumoniae, a pneumococcal adhesin SpsA hijacks SIgA and unliganded pIgR/SC to evade host defense and gain entry to human cells. How SpsA specifically targets SIgA and pIgR/SC also remains unclear. Here we report a cryo-electron microscopy structure of the Fc region of human IgA1 (Fcα) in complex with J-chain and SC (Fcα-J-SC), which reveals the organization principle of SIgA. We also present the structure of Fcα-J-SC in complex with SpsA, which uncovers the specific interaction between SpsA and human pIgR/SC. These results advance the molecular understanding of SIgA and shed light on the pathogenesis of S. pneumoniae.

scholarly journals INFLUENCE OF LACTOBACILLUS SPP. ON COLONIZATION AND ANTI-INFECTIOUS RESISTANCE OF THE MUCOUS MEMBRANES OF THE UPPER RESPIRATORY TRACT

2017 ◽  
Author(s):  
S. V. Kalinichenko ◽  
O. O. Korotkykh ◽  
S. I. Pokhil ◽  
M. G. Bakumenko
Keyword(s):  
Staphylococcus Aureus ◽  
Respiratory Tract ◽  
Immunoglobulin A ◽  
Secretory Immunoglobulin A ◽  
Upper Respiratory Tract ◽  
Colonization Resistance ◽  
Mucous Membranes ◽  
Upper Respiratory ◽  
Lactobacillus Spp ◽  
Secretory Immunoglobulin

Background. Lactobacilli are very important for the formation of colonization resistance and have pronounced antagonistic effect against a wide range of microorganisms. That is why the lactobacilli have extensive use as a component of classic probiotic agents that are widely used to prevent and treat dysbiotic conditions of digestive and genital systems of people.Objective. The aim of the research was to study the effect of lactobacilli on anti-infectious resistance of mucous membranes of upper respiratory tract.Methods. The colonization degree (lg CFU / g) of nasal mucosal membranes by Lactobacillus spp. and S. aureus was determined in all carriers before the experiment. Also, the level of lysozyme and secretory immunoglobulin A (sIgA) in nasal secretions cavities was identified.Results. It was established a clear dysfunction of anti-infectious resistance in carriers of Staphylococcus aureus - a decrease of colonization resistance and local immunity of mucous membranes of upper respiratory tract. As for the anti-infectious resistance of nasal mucosal of S. aureus carriers, the level of lysozyme and secretory immunoglobulin A gradually increased after the application of probiotic strain L. rhamnosus GG, and in 21 days it reached rates of healthy individuals.Conclusions. It was found out that probiotics for nasal passages sanitation in Staphylococcus aureus carriers lead to gradual eradication of the pathogen (S. aureus) with restoration of colonization and anti-infectious resistance, mucous membranes and upper respiratory tract.

scholarly journals The Polysaccharides from Codonopsis pilosula Modulates the Immunity and Intestinal Microbiota of Cyclophosphamide-Treated Immunosuppressed Mice

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1801 ◽  
Author(s):  
Yu-Ping Fu ◽  
Bin Feng ◽  
Zhong-Kai Zhu ◽  
Xin Feng ◽  
Shu-Fan Chen ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Immunoglobulin A ◽  
Control Group ◽  
Group Model ◽  
Codonopsis Pilosula ◽  
Model Control ◽  
Model Control Group ◽  
Ifn Γ ◽  
Immunosuppressed Mice ◽  
Secretory Immunoglobulin

Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of Lactobacillus and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.

scholarly journals An IgA mimicry of IgG that binds polymeric immunoglobulin receptor for mucosa transcytosis

2020 ◽  
Vol 3 (3) ◽  
pp. 157-162
Author(s):  
Changchuin Mao ◽  
Richard Near ◽  
Varuna Shibad ◽  
Xuemei Zhong ◽  
Wenda Gao
Keyword(s):  
Diphtheria Toxin ◽  
Immunoglobulin A ◽  
Binding Activity ◽  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
Diphtheria Toxin Receptor ◽  
Toxin Receptor ◽  
Immune Exclusion ◽  
Compact Design ◽  
First Time

Abstract Most pathogens establish infection through mucosa, where secretory immunoglobulin A (sIgA) plays an ‘immune exclusion’ role in humoral defense. Extravasation of intravenously (i.v.) administrated therapeutic immunoglobulin G (IgG) mainly relies on convection and/or neonatal Fc receptor-mediated transcytosis from circulation into interstitial space. Active transport of interstitial IgG further across epithelium into mucosa, like sIgA, is a much desired feature for the next generation of therapeutic antibodies, especially for anti-infection purposes. For the first time, we report the engineering of an IgA mimicry of IgG, with its Fc portion in fusion with the 18-aa tail piece (tp) of sIgA and the J chain, possessing sIgA’s full binding activity towards polymeric immunoglobulin receptor that mediates mucosa transcytosis. In a diphtheria toxin receptor (DTR) knockin mouse model, i.v. injected anti-diphtheria toxin (DT) IgG(tp)J protected DTR+ cells from deletion upon DT injection. The compact design of IgG(tp)J opens new revenues for more effective therapeutic IgG mimicking some of the important biological functions of IgA.

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