2021
DOI: 10.3389/fcimb.2020.593823
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Mechanisms of Effector-Mediated Immunity Revealed by the Accidental Human Pathogen Legionella pneumophila

Abstract: Many Gram-negative bacterial pathogens employ translocated virulence factors, termed effector proteins, to facilitate their parasitism of host cells and evade host anti-microbial defenses. However, eukaryotes have evolved to detect effector-mediated virulence strategies through a phenomenon termed effector-triggered immunity (ETI). Although ETI was discovered in plants, a growing body of literature demonstrates that metazoans also utilize effector-mediated immunity to detect and clear bacterial pathogens. This… Show more

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Cited by 10 publications
(7 citation statements)
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References 111 publications
(168 reference statements)
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“…pneumophila replication within macrophages is a direct consequence of extensive co-evolution with natural host amoebae [ 7 9 ]; however, L . pneumophila rarely transmits person-to-person and is rapidly cleared by acute pathogen-centric innate immune responses in healthy hosts [ 10 12 ]. To establish its intracellular niche, the Legionella -containing vacuole (LCV), L .…”
Section: Introductionmentioning
confidence: 99%
“…pneumophila replication within macrophages is a direct consequence of extensive co-evolution with natural host amoebae [ 7 9 ]; however, L . pneumophila rarely transmits person-to-person and is rapidly cleared by acute pathogen-centric innate immune responses in healthy hosts [ 10 12 ]. To establish its intracellular niche, the Legionella -containing vacuole (LCV), L .…”
Section: Introductionmentioning
confidence: 99%
“…Indeed, a growing number of effectors are linked to effector-triggered immunity due to different connectivity of their targets with host cell physiology in amoeba and in mammalian host cells (reviewed by [339]). The effector LegC4 promotes replication in amoeba but triggers increased cytokine release leading to growth restriction in murine macrophages [340].…”
Section: Modulation Of Autophagy and Other Cell Autonomous Defence Me...mentioning
confidence: 99%
“…To establish its intracellular niche, the Legionella-containing vacuole (LCV), L. pneumophila employs hundreds of virulence factors, called effector proteins, that are translocated into infected host cells by a Dot/Icm type IV secretion system (T4SS) (6). Effectors are essential for virulence, but their activity can also trigger upregulation of pro-inflammatory cytokine production by infected macrophages via effector-triggered immunity (ETI) (7)(8)(9). We discovered that the L. pneumophila effector LegC4, which is a bona fide virulence factor in amoebae, confers a fitness disadvantage on L. pneumophila in a mouse model of Legionnaires' Disease (10).…”
Section: Introductionmentioning
confidence: 99%
“…To establish its intracellular niche, the Legionella -containing vacuole (LCV), L. pneumophila employs hundreds of virulence factors, called effector proteins, that are translocated into infected host cells by a Dot/Icm type IV secretion system (T4SS) (Chauhan and Shames, 2021). Effectors are essential for virulence, but their activity can also trigger upregulation of pro-inflammatory cytokines by infected macro-phages via effector-triggered immunity (ETI) (Asrat et al, 2014; Fischer et al, 2019; Fontana et al, 2011; Ngwaga et al, 2021). Pro-inflammatory cytokines are central to clearance of L. pneumophila by healthy hosts, since they activate and potentiate the antimicrobial capacity of infected macrophages.…”
Section: Introductionmentioning
confidence: 99%