Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

Area of Science:

• Immunology
• Microbiology
• Pathogenesis

Background:

• Neutrophils play a crucial role in host defense against bacterial infections.
• NETosis, a form of programmed cell death in neutrophils, releases neutrophil extracellular traps (NETs) to ensnare and kill pathogens.
• Leptospira spp. are pathogenic bacteria that cause leptospirosis, a zoonotic disease with significant global health implications.

Purpose of the Study:

• To investigate the capacity of Leptospira spp. to induce NETosis.
• To elucidate the role of NETosis in the host response to Leptospira infection in vivo.
• To determine the impact of NETosis on bacterial dissemination and host pathology.

Main Methods:

• Human neutrophils were incubated ex vivo with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC).
• Murine models were used to study NETosis in vivo following LIC infection.
• Microscopy, fluorometry, and neutrophil depletion using mAb1A8 were employed to analyze NET formation and its consequences.

Main Results:

• LIC induced NETosis in human neutrophils, with bacterial number, pathogenicity, and viability being key factors.
• Entrapment of LIC within NETs led to bacterial death, although pathogenic Leptospira sp. degraded DNA via nucleases.
• Mice infected with LIC exhibited circulating NETs, and neutrophil depletion resulted in increased bacteremia and higher kidney bacterial burden.
• Early stages of infection showed low bacterial burden, few neutrophils, and minimal inflammation in kidneys and liver, despite similar interstitial nephritis severity in depleted and non-depleted mice.

Conclusions:

• Leptospira interrogans (LIC) effectively triggers NETosis, leading to the formation of neutrophil extracellular traps (NETs).
• Intravascular NET formation is critical for limiting early dissemination of LIC and reducing overall bacterial burden.
• NETosis plays a significant role in controlling Leptospira infection, despite the bacteria's capacity for DNA degradation.