Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Leptospirosis is an emerging infectious disease with recent outbreaks in California and New York.
• Understanding the host immune response, particularly cell death pathways, is crucial for managing leptospirosis.

Purpose of the Study:

• To investigate the role of apoptosis and necroptosis in the inflammatory response to Leptospira infection.
• To characterize the specific cell types affected by these programmed cell death pathways.

Main Methods:

• Mice were infected with pathogenic (L. interrogans) and non-pathogenic (L. biflexa) Leptospira.
• Flow cytometry was used to analyze apoptosis and necroptosis in spleen cells.
• Western blot assessed the expression of necroptosis biomarkers (p-MLKL, p-RIP1, p-RIP3).

Main Results:

• Pathogenic L. interrogans induced apoptosis in neutrophils and monocytes at 24h and 72h.
• L. interrogans also induced necroptosis in neutrophils, monocytes, and macrophages.
• Non-pathogenic L. biflexa induced apoptosis and necroptosis in a more limited manner, primarily at 24h.
• Increased expression of necroptosis biomarkers was observed with pathogenic L. interrogans infection.

Conclusions:

• Early apoptosis and necroptosis of myeloid cells are key features of the immune response to pathogenic Leptospira.
• These cell death processes may explain the reduced frequency of certain immune cells in the spleen.
• Cell death pathways contribute to persistent inflammation in early-stage leptospirosis.