Transbronchial Invasion and Proliferation of Leptospira interrogans in Lung without Inflammatory Cell Infiltration in a Hamster Model

ABSTRACT

Leptospirosis caused by pathogenic Leptospira is one of the most common zoonoses in the world. It is believed that humans become infected with it mainly through their skin and mucous membranes by contact with water or soil that is contaminated with urine excreted from infected animals. Recently, outbreaks have frequently occurred in the tropics, especially after flooding, but how leptospires cause mass infection remains poorly understood. In this study, we injected leptospires into the tracheas of hamsters under direct view and prove for the first time that leptospires can infect through the respiratory tract. We determined that a 50% lethal dose (LD₅₀) of the Leptospira interrogans strain UP-MMC-SM (L495) for hamsters in transtracheal infection was 3.2 × 10² cells. The results of culture, macroscopic findings, and histopathological analysis suggested that intratracheally injected leptospires invaded the lung tissue, proliferated in the collagen-rich stroma adjacent to the bronchus and blood vessels, and then spread throughout the body via the bloodstream. In the lung, leptospires continuously infiltrated the alveolar wall without inflammatory cell infiltration, spread throughout the lung, and finally caused pulmonary hemorrhage. Our results revealed that the respiratory tract might be a portal of entry for leptospires. We speculate that some cases of leptospirosis might be caused by transbronchial infection from inhaling infectious aerosols containing leptospires during floods. Leptospira was also confirmed to be a unique pathogen that invades through the bronchus, proliferates in the collagen-rich lung stroma, and spreads through the alveolar interstitium throughout the lung without causing pneumonia.