Human white blood cells’ self-defense against haemolytic infection

15 Jan 2015. NUS scientists have discovered how the human white blood cells react for self-preservation during a haemolytic infection, which lyses red blood cells, releasing cytotoxic haemoglobin (Hb) into the plasma.

Recent studies showed that immune cells recognize redox-active cytotoxic extracellular Hb (metHb)bound to pathogen-associated molecular patterns (PAMPs), and the available information is limited to experiments performed in defined conditions using single cell lines. Therefore, a systemic approach targeting primary whole blood cells is required to better understand the cellular immune defence against metHb and PAMPs, when it is under a haemolytic infection.

A team led by Prof DING Jeak Ling from the Department of Biological Sciences in NUS found that metHb activates NFk-B in TLR2-expressing HEK293 cells but not in normal or TLR9-expressing HEK293 cells. Treatment of isolated neutrophils with metHb increased production of ROS and expressions of IL-8, TNFa, and CD11b, which were further enhanced by metHb+LTA complex. While LTA stimulated the survival of neutrophils, it caused apoptotic cell death when complexed with metHb.The activation of neutrophils by metHb+LTA was subdued by the presence of other types of white blood cells. The team’s findings indicate that metHb and metHb+LTA complex are ligands of TLR2, inducing an unconventional TLR signalling pathway. Neutrophils are a highly sensitive cell type responsive to metHb+LTA complex. During a haemolytic infection, white blood cells in the vicinity crosstalk to modulate neutrophil TLR-signalling induced by metHb and LTA (see Figure).

This research has been published in EBioMedicine, an Open Access journal with Cell Press and The Lancet editorial influence.

DingJL 1

This image shows that during a haemolytic infection, white blood cells in the vicinity crosstalk to modulate neutrophil TLR-signalling induced by metHb and LTA. [Image credit: Sae-Kyung LEE]

Reference

Lee SK, Goh SY, Wong YQ, Ding JL. "Response of neutrophils to extracellular haemoglobin and LTA in human blood system " EBioMedicine (2015) doi.org/10.1016/j.ebiom.2015.01.003