September 12, 2022

Enhancing innate immunity in the lung

Vanderbilt researchers show that a TLR4 agonist improves lung immune response and survival in a mouse model of bacterial pneumonia, supporting the development of this drug to protect against pneumonia in hospitalized patients.

Critically ill, surgical and elderly patients are vulnerable to nosocomial pneumonia and other hospital-acquired infections that increase morbidity and mortality. With growing antibiotic resistance of nosocomial pathogens, there is a need for novel therapeutics to manage infections. 

Antonio Hernandez, MD, MSCI, and colleagues are exploring the use of TLR4 agonists to induce “trained immunity” — a heightened response of innate leukocytes (white blood cells) to subsequent infection. 

Using a clinically relevant mouse model of pneumonia, they gave mice lung treatments of 3D PHAD (a TLR4 agonist) for two days, then challenged the lungs with Klebsiella pneumoniae bacteria. Mice that received 3D PHAD had enhanced recruitment of innate leukocytes to the lungs, improved bacterial clearance, decreased pneumonia and improved survival compared to control mice. 

The findings, reported in the journal Shock, show that 3D PHAD augments innate immunity in the lung and has potential for development as an immunotherapeutic agent to protect against pneumonia.

Other authors of the study include Jing Zhou, Julia Bohannon, PhD, Margaret McBride, Katherine Gibson-Corley, DVM, PhD, Naeem Patil, MBBS, PhD, Allison Owen, PhD, Katherine Burelbach, and Edward Sherwood, MD, PhD. The research was supported by grants from the National Institutes of Health (GM123345, GM121711, GM141927, GM119197, AI151210, GM108554).