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Multifunctional role of human SPLUNC1 in Pseudomonas aeruginosa infection
Sameera Sayeed1, Laura Nistico, Claudette St Croix
1Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
The human short PLUNC1 (SPLUNC1) protein has been identified as a component of the pulmonary antimicrobial response based on its structural similarity to the bactericidal/permeability-increasing (BPI) protein. Using a genetically modified mouse model, we recently verified the antimicrobial activity of SPLUNC1 against Pseudomonas aeruginosa in vivo. To further define the mechanism of epithelial SPLUNC1-mediated antibacterial action, we carried out studies to determine how SPLUNC1 protects the host from acute respiratory infections. P. aeruginosa treated with recombinant human SPLUNC1 protein showed decreased growth in vitro. This antibacterial activity was due to growth inhibition, as a consequence of a SPLUNC1-induced increase in bacterial cell permeability. Removal of SPLUNC1 allowed the recovery of P. aeruginosa and suggested no permanent cell injury or direct killing of bacteria. Further investigation showed coating of bacterial cells by SPLUNC1. We suggest that this "bacterial cell coating" is necessary for the bacteriostatic function of SPLUNC1. Additionally, we demonstrated a novel role for SPLUNC1 as a chemoattractant that facilitated migration of macrophages and neutrophils. Taking the findings together, we propose synergistic roles for human SPLUNC1 as an antibacterial agent with bacteriostatic and chemotactic activities.
Insights
Human short PLUNC1 (SPLUNC1) protein inhibits Pseudomonas aeruginosa growth by increasing bacterial cell permeability. SPLUNC1 also acts as a chemoattractant, enhancing immune cell migration for a combined antimicrobial effect.
Area of Science:
- Pulmonary immunology
- Microbiology
- Host-pathogen interactions
Background:
- The human short PLUNC1 (SPLUNC1) protein is structurally similar to bactericidal/permeability-increasing (BPI) protein and is involved in the pulmonary antimicrobial response.
- Previous studies verified SPLUNC1's in vivo antimicrobial activity against Pseudomonas aeruginosa.
Purpose of the Study:
- To elucidate the mechanism of epithelial SPLUNC1-mediated antibacterial action in acute respiratory infections.
- To define the specific roles of SPLUNC1 in host defense against bacterial pathogens.
Main Methods:
- In vitro studies using recombinant human SPLUNC1 protein and Pseudomonas aeruginosa cultures.
- Assessment of bacterial growth, cell permeability, and bacterial cell surface interactions.
- Evaluation of SPLUNC1's chemoattractant properties for immune cells (macrophages and neutrophils).
Main Results:
- Recombinant human SPLUNC1 protein demonstrated bacteriostatic activity against P. aeruginosa in vitro by increasing bacterial cell permeability.
- SPLUNC1 treatment resulted in bacterial cell coating, which was essential for its growth-inhibiting function.
- SPLUNC1 exhibited a novel chemoattractant role, promoting macrophage and neutrophil migration.
Conclusions:
- Human SPLUNC1 possesses synergistic antibacterial properties, acting as both a bacteriostatic agent and a chemoattractant.
- SPLUNC1 contributes to host defense by inhibiting bacterial growth and recruiting immune cells to infection sites.
- These findings highlight SPLUNC1's multifaceted role in managing acute respiratory infections.
