Transbronchial Invasion and Proliferation of Leptospira interrogans in Lung without Inflammatory Cell Infiltration in
Yasuhiko Nikaido1,2, Midori Ogawa3, Kazumasa Fukuda3
1Department of Microbiology, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan yasuhiko@nikaido.jp.
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.
Insights
Leptospirosis, a common zoonotic disease, can infect humans through the respiratory tract. This study shows pathogenic Leptospira invade the lungs, spread via the bloodstream, and cause hemorrhage, suggesting inhalation is a key infection route.
Area of Science:
- Infectious Diseases
- Microbiology
- Pathogen Biology
Background:
- Leptospirosis is a widespread zoonotic disease, typically acquired through skin/mucous membrane contact with contaminated environments.
- Recent outbreaks in tropical regions, particularly after floods, highlight gaps in understanding transmission dynamics.
- The primary route of human infection is traditionally considered dermal or mucosal exposure.
Purpose of the Study:
- To investigate the respiratory tract as a potential portal of entry for pathogenic Leptospira.
- To elucidate the mechanism of Leptospira infection and dissemination following respiratory exposure.
- To determine the lethal dose of Leptospira interrogans via transtracheal inoculation in a hamster model.
Main Methods:
- Transtracheal inoculation of hamsters with Leptospira interrogans strain UP-MMC-SM (L495) under direct visualization.
- Determination of the 50% lethal dose (LD50) for transtracheal infection.
- Analysis of infection progression using culture, macroscopic examination, and histopathological evaluation.
Main Results:
- Pathogenic Leptospira successfully infected hamsters via the respiratory tract, with an LD50 of 3.2 × 10^2 cells.
- Intratracheal inoculation led to Leptospira invasion, proliferation in lung stroma near bronchi and blood vessels, and subsequent systemic spread.
- Leptospira infiltrated alveolar walls without causing significant inflammatory cell infiltration, leading to pulmonary hemorrhage and dissemination throughout the lungs.
Conclusions:
- The respiratory tract is identified as a potential portal of entry for Leptospira.
- Inhalation of infectious aerosols containing Leptospira during floods may cause transbronchial infection and subsequent leptospirosis.
- Leptospira exhibits unique pathogenic behavior by invading the bronchus, proliferating in lung stroma, and spreading interstitially without inducing pneumonia.
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