Leptospira species promote a pro‐inflammatory phenotype in human neutrophils

• Published in: Cellular microbiology Vol. 21; no. 2; pp. e12990 - n/a
• Main Authors: Charo, Nancy, Scharrig, Emilia, Ferrer, María F., Sanjuan, Norberto, Carrera Silva, Eugenio A., Schattner, Mirta, Gómez, Ricardo M.
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01-02-2019
• Subjects: Antibodies; Apoptosis; Axl protein; Blocking antibodies; CD11b antigen; CD11b Antigen - metabolism; Cell activation; Collagen; degranulation; Diagnostic systems; granulocytes; Human behavior; Humans; Inflammasomes; Inflammation; Inflammatory response; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Kinases; Leptospira; Leptospira - immunology; Leptospira biflexa; Leptospira interrogans; Leptospira interrogans - immunology; Leptospirosis; Leptospirosis - immunology; Leptospirosis - microbiology; Leptospirosis - pathology; Leukocyte migration; Leukocytes (neutrophilic); Neutrophil Activation - immunology; Neutrophils; Neutrophils - immunology; NF-κB protein; phagocytosis; Phenotypes; polymorphonuclear cells; Protein-tyrosine kinase receptors; Proteins; TLR2 protein; TLR4 protein; Toll-like receptors; Tyrosine; Zoonoses; granulocytes; phagocytosis; polymorphonuclear cells; Leptospira interrogans; degranulation; Leptospira biflexa
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/cmi.12990

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.