First observation of neutrophil extracellular traps in human leptospirosis

Scharrig, Emilia; Drut, Ricardo; Gómez, Ricardo Martín

doi:10.5430/crcp.v4n4p10

Cited by 2 publications

(2 citation statements)

References 9 publications

(15 reference statements)

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“…Also, levels of circulating nucleosomes were increased after infection but decreased in neutrophil‐depleted mice (Scharrig et al, ). In addition, the presence of NETs was observed in lung tissue in one human case (Scharrig, Drut, & Gómez, ). These findings, together with our ultrastructural observations showing that LIC was rarely phagocytized and that the main microbicide substances, such as MPO and ROS, are not produced by LIC suggest that neutrophils sense pathogenic Leptospira spp.…”

Section: Discussionmentioning

confidence: 94%

Leptospiraspecies promote a pro‐inflammatory phenotype in human neutrophils

Charó

Scharrig

Ferrer

et al. 2018

Cellular Microbiology

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Leptospirosis is a global zoonosis caused by pathogenic Leptospira. Neutrophils are key cells against bacterial pathogens but can also contribute to tissue damage. Because the information regarding the role of human neutrophils in leptospirosis is scant, we comparatively analysed the human neutrophil's response to saprophytic Leptospira biflexa serovar Patoc (Patoc) and the pathogenic Leptospira interrogans serovar Copenhageni (LIC). Both species triggered neutrophil responses involved in migration, including the upregulation of CD11b expression, adhesion to collagen, and the release of IL‐8. In addition, both species increased levels of pro‐inflammatory IL‐1β and IL‐6 associated with the inflammasome and NFκB pathway activation and delayed neutrophil apoptosis. LIC was observed on the neutrophil surface and not phagocytized. In contrast, Patoc generated intracellular ROS associated with its uptake. Neutrophils express the TYRO3, AXL, and MER receptor protein tyrosine kinases (TAM), but only LIC selectively increased the level of AXL. TLR2 but not TLR4‐blocking antibodies abrogated the IL‐8 secretion triggered by both Leptospira species. In summary, we demonstrate that Leptospira species trigger a robust neutrophil activation and pro‐inflammatory response. These findings may be useful to find new diagnostic markers and therapeutic strategies against leptospirosis.

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Section: Discussionmentioning

confidence: 94%

Leptospiraspecies promote a pro‐inflammatory phenotype in human neutrophils

Charó

Scharrig

Ferrer

et al. 2018

Cellular Microbiology

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“…A higher number of circulating neutrophiles has been reported during human leptospirosis [ 59 ] and NETosis has been implicated in leptospires killing [ 60 , 61 ], but pathogenic Leptospira remain at the surface of neutrophiles without triggering ROS production by MPO [ 62 ]. Interestingly, the non-pathogenic strain, L. biflexa , exhibit a different behavior in the same condition as they were found inside phagocytic vacuoles of neutrophiles and they triggered ROS production [ 62 ].…”

Section: Are Leptospira Exposed To Ros In Their Di...mentioning

confidence: 99%

The Arsenal of Leptospira Species against Oxidants

Huete

Benaroudj

2023

Antioxidants

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Reactive oxygen species (ROS) are byproducts of oxygen metabolism produced by virtually all organisms living in an oxic environment. ROS are also produced by phagocytic cells in response to microorganism invasion. These highly reactive molecules can damage cellular constituents (proteins, DNA, and lipids) and exhibit antimicrobial activities when present in sufficient amount. Consequently, microorganisms have evolved defense mechanisms to counteract ROS-induced oxidative damage. Leptospira are diderm bacteria form the Spirochaetes phylum. This genus is diverse, encompassing both free-living non-pathogenic bacteria as well as pathogenic species responsible for leptospirosis, a widespread zoonotic disease. All leptospires are exposed to ROS in the environment, but only pathogenic species are well-equipped to sustain the oxidative stress encountered inside their hosts during infection. Importantly, this ability plays a pivotal role in Leptospira virulence. In this review, we describe the ROS encountered by Leptospira in their different ecological niches and outline the repertoire of defense mechanisms identified so far in these bacteria to scavenge deadly ROS. We also review the mechanisms controlling the expression of these antioxidants systems and recent advances in understanding the contribution of Peroxide Stress Regulators in Leptospira adaptation to oxidative stress.

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First observation of neutrophil extracellular traps in human leptospirosis

Cited by 2 publications

References 9 publications

Leptospiraspecies promote a pro‐inflammatory phenotype in human neutrophils

Leptospiraspecies promote a pro‐inflammatory phenotype in human neutrophils

The Arsenal of Leptospira Species against Oxidants

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