Real-time near-infrared imaging distinguishes nasopharyngeal colonization from aspiration of Streptococcus pneumoniae and identifies aspiration as a trigger of severe disease

Streptococcus pneumoniae can reside harmlessly in the nasal passages, but it can also invade the lungs, causing severe illness, particularly in elderly individuals. Researchers have now created a real-time imaging technique using near-infrared fluorescence to track the bacteria's early distribution. This method involves tagging S. pneumoniae with indocyanine green (ICG) without altering its growth or tolerance.

By observing the bacteria in live video recordings within the first 10 minutes of infection, the scientists identified two patterns: bacteria confined to the nasal cavity (colonization) and bacteria aspirated into the lower respiratory tract (aspiration).

Analyzing data from both young and aged mice, the researchers found that aspiration resulted in significantly higher mortality rates in both age groups, with a hazard ratio of 7.9 for young mice and 8.4 for aged mice. This held true even when a minimal amount of bacteria, 10 times less than the amount given to young mice, was used for the aged group. By day 3, deaths began to occur.

Further investigation revealed that early aspiration in aged mice triggered a series of inflammatory and hematopoietic responses, as well as activation of complement and coagulation cascades, and phagocytic pathways, when analyzed through blood samples taken at 24 hours post-infection via RNA sequencing and plasma proteomics. These findings demonstrate that aspiration into the lower respiratory tract of S. pneumoniae is a critical factor in the development of severe pneumococcal disease.

The researchers have also demonstrated a real-time NIR imaging technique that links early infection dynamics to systemic host responses, providing a valuable tool for understanding the progression of pneumococcal disease.