Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis.

Xu Chen,Wei-Lin Hu,Jie Yan,Shi-Jun Li,Xu’Ai Lin,David M Ojcius,Ai-Hua Sun

doi:10.1371/journal.pone.0181014

Abstract

ObjectiveTo identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans.MethodsMajor infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry.ResultsPeripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver and kidneys of infected mice. Levels of macrophage- but not neutrophil-specific chemokines and VECAMs were significantly increased in the samples from infected mice and patients. All macrophages tested had a higher ability than neutrophils to phagocytose and kill leptospires. Higher ROS and NO levels and [Ca2+]i in the macrophages were involved in killing leptospires. Human macrophages displayed more phagolysosome formation and a stronger leptospire-killing ability to than mouse macrophages.ConclusionsMononuclear-macrophages but not neutrophils represent the main infiltrating and anti-leptospiral phagocytes during leptospirosis. A lower level of phagosome-lysosome fusion may be responsible for the lower Leptospira-killing ability of human macrophages.

Highlights

Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species [1]
Levels of macrophage- but not neutrophil-specific chemokines and vascular endothelial cell adhesion molecules (VECAMs) were significantly increased in the samples from infected mice and patients
The confocal microscopic examination confirmed that the number of leptospires in the L. interrogansinfected Hu- or Ms-macrophages was significantly higher than in the L. interrogans-infected Hu- or Ms-neutrophils (Fig 1A and 1B)

Summary

Introduction

Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species [1]. In recent years, human leptospirosis has been considered as an emerging infectious disease in Europe and North America [6,7,8]. Over one million human leptospirosis cases have been reported annually, and the mortality rate ranges from 5 to 20% worldwide [9]. Many animals, such as livestock and rodents, serve as the hosts of pathogenic Leptospira species, and most the infected animals continuously discharge leptospires through their urine to contaminate soil and water [10]. Human leptospirosis is present in an extremely broad clinical spectrum ranging from mild influenza-like illness to severe life-threatening forms characterized by high fever, myalgia and jaundice, to pulmonary diffuse hemorrhage, meningitis and renal failure [10,11,12]

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