Leptospira interrogans enters different host cells by binding to distinct molecules in the extracellular matrix

Xin Zhao,Jie Yan,Huan Wang,Yu-Mei Ge,Ai-Hua Sun

doi:10.2298/abs140702003z

Abstract

Leptospirosis caused by Leptospira is a worldwide zoonotic disease. The 2 spirochete can efficiently invade host cells and spread from blood into internal organs, but the mechanisms of leptospiral internalization into different host cells remain poorly understood. Adhesion of leptospires to the ECM (extracellular matrix) initiated leptospire internalization in macrophage cell-lines THP-1, J774A.1, and in human umbilical epithelial cells (HUVEC). We assessed the distribution of ECM , including fibronectin (FN), laminin and collagens 1-4 (COL1-COL4) in different cells. FN was expressed in THP-1 and J774A.1 cells, and FN, LN, COL3 and COL4 were expressed in HUVEC. Then, we found leptospires adhered to FN, LN, COL3 and COL4. The most important intracellular leptospires in macrophages (THP-1 and J774A) significantly decreased when leptospires were pre-blocked with FN This indicates that FN has an important role in the adherence to and entry of leptospires in macrophages, while in HUVEC, FN, LN, COL3 and COL4 assume this role.

Highlights

Leptospirosis is a worldwide disease that is lethal to some mammals
Quantitative ELISA demonstrated that the number of FN molecules per cell expressed by the THP-1 and J774A.1 cells was about 4.2×107 and 3.8×107, respectively, while the human umbilical vein endothelial cell line (HUVEC) expressed 1.5×107 FN, 1.2×106 LN, 2.7×106 COL3, and 3.1×107 COL4 molecules per cell (Fig. 3)
The data reveal the large diversity of ECM molecules expressed by macrophages and vascular endothelial cells as well as the strong ability of L. interrogans to adhere to host cells through a combination of different ECM molecules

Summary

Introduction

Leptospirosis is a worldwide disease that is lethal to some mammals. Leptospires penetrate the mucosal tissues and skin of mammals such as humans and mice, and are transported by the blood to different organs, including the liver, lungs and kidneys (Goncalves-de-Albuquerque et al, 2012). The symptoms of leptospirosis in humans vary from mild to fatal, ranging from high fever with muscle pain to severe symptoms such as pulmonary hemorrhage, jaundice and meningitis, which lead to respiratory failure and renal failure with high mortality rates (Zhang et al, 2012a; Pappas et al, 2008). Different cell-types play different roles when infected by pathogens. Macrophages assume a crucial role in phagocytosis and killing pathogens by degradation. Vascular endothelial cells are responsible for the transport of pathogens from the blood stream to target organs as both macrophages and vascular endothelial cells uptake leptospires during infection

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