Mechanism of invasion of lung epithelial cells by filamentous Legionella pneumophila.
Legionella, the aetiological agent responsible for Legionellosis, is an opportunistic pathogen that infects humans upon the inhalation of contaminated aerosolized water droplets. Legionella is pleomorphic and its different morphotypes exhibit varying degrees of virulence. While the filamentous forms of Legionella pneumophila (Lp) have been reported in patient samples since the first description of legionellosis, their role in disease has not been studied. Our results show that both E-cadherin and β1 integrin receptors mediate filamentous Lp (FLp) attachment to lung epithelial cells (LECs). The activation of these receptors induces the formation of actin enriched membrane surface structures that we designated 'hooks' and 'membrane wraps'. These structures entrap the filaments on the cell surface leading to their gradual internalization through a zipper mechanism of phagocytosis dependent on actomyosin activity. The supply of E-cadherin receptors from the recycling pathway and β1 integrins released from focal adhesion turnover are required to sustain this process. Intracellular FLp inhabits a vacuolar compartment where filaments differentiate into short rods and replicate to produce infective progeny. Here we are reporting a first description of the invasion mechanism used by FLp to invade LECs. Therefore, filamentous morphotype of Lp can induce its own uptake by LECs and has the potential ability to cause disease.
Department of Biological Sciences, University of Toronto at Scarborough, Toronto, ON, Canada.
Akriti
A
Prashar
Sonam
S
Bhatia
Zohreh
Z
Tabatabaeiyazdi
Carla
C
Duncan
Rafael A
RA
Garduño
Patrick
P
Tang
Donald E
DE
Low
Cyril
C
Guyard
Mauricio R
MR
Terebiznik
D000205:Actomyosin / Q000378:metabolism; D001422:Bacterial Adhesion; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D016952:Legionella pneumophila / Q000166:cytology / Q000472:pathogenicity*; D010587:Phagocytosis; D011485:Protein Binding
D015820:Cadherins; D019012:Integrin beta1; D000205:Actomyosin