Pathogenicity and Virulence ofLegionella: Intracellular replication and host response

Abstract

Bacteria of the genus Legionella are natural pathogens of amoebae that can cause a severe pneumonia in humans called Legionnaires’ Disease. Human disease results from inhalation of Legionella -contaminated aerosols and subsequent bacterial replication within alveolar macrophages. Legionella pathogenicity in humans has resulted from extensive co-evolution with diverse genera of amoebae. To replicate intracellularly, Legionella generates a replication-permissive compartment called the Legionella -containing vacuole (LCV) through the concerted action of hundreds of Dot/Icm-translocated effector proteins. In this review, we present a collective overview of Legionella pathogenicity including infection mechanisms, secretion systems, and translocated effector function. We also discuss innate and adaptive immune responses to L. pneumophila , the implications of Legionella genome diversity and future avenues for the field.

Legionella pneumophila—Epidemiology and Characterization of Clinical Isolates, Slovenia, 2006–2020

“…In hospitals, the important route of infection is microaspiration of drinking water contaminated with Legionella or by direct incorporation into the lung during respiratory tract manipulation [ 2 , 3 ]. After Legionella enters the pulmonary alveoli, it is phagocytosed by macrophages, where exponential replication occurs [ 4 ]. Such an infection leads to the development of Legionnaires’ disease (LD), a severe, life-threatening pneumonia, or to a flu-like illness called Pontiac fever.…”

TNF-α response in macrophages depends on clinical Legionella pneumophila isolates genotypes

“…In addition, LegK1 and LnaB activate NF-κB signaling pathway, which controls the transcription of pro-inflammatory but also pro-survival genes [ 34 , 35 ], and, more recently, it was reported that LegC4 increases TNF-α secretion from murine bone-marrow-derived macrophages and contributes to Lp clearance [ 36 ]. Beside the Dot/Icm T4SS, it was established in mice that TNF-α is produced in response to Lp in a flagellin-independent manner [ 37 ] but other pathogen-associated molecular patterns (PAMPs) like lipopolysaccharide, lipoproteins, or dsDNA could be involved [ 2 , 13 ]. Taken together, these effectors and PAMPs constitute interesting candidates, and future studies should evaluate if they are differentially regulated or constituted between ST1 and ST47 isolates.…”

“…Legionella pneumophila (Lp) is a Gram-negative bacterium that replicates within eukaryotic microorganisms in aquatic ecosystems [ 1 , 2 ]. It can be an accidental human pathogen if contaminated droplets from colonized man-made water systems are inhaled.…”

“…It can be an accidental human pathogen if contaminated droplets from colonized man-made water systems are inhaled. In the lungs, after phagocytosis by alveolar macrophages, Lp rapidly injects around 300 effectors via a Dot/Icm type IV secretion system (T4SS) in order to avoid destruction, hijack the host’s defenses, and create its replicative vacuole [ 1 , 2 ]. The resulting infection is a severe pneumonia named Legionnaires’ disease (LD).…”

Exploring the Individual Bacterial Microbiota of Questing Ixodes ricinus Nymphs

“…One is a metagenomic analysis of the pathobiome of Haemaphysalis longicornis (adults, nymphs and larvae) collected on Staten Island in the United States [ 96 ], and the other is a pyrosequencing analysis of the microbiota of Hyalomma [ 97 ]. This is of interest since several species are known to be pathogenic to humans [ 98 ]. Moreover, these bacteria and their natural vectors (phagotrophic protists) are ubiquitous in humid soils and thus can share a common habitat with ticks that are sensitive to desiccation and require an important hygrometry [ 99 ].…”