Activation of human neutrophils by the polysaccharide chitin

Introduction:

Some pathogenic fungi cause severe invasive infections. The innate immune system recognizes fungal cell wall molecules, triggering immune responses and adaptive immunity, particularly involving neutrophils. Neutrophils, which detect pathogen-associated molecular patterns (PAMPs), can form neutrophil extracellular traps (NETs), with or without reactive oxygen species (ROS). Fungal patterns like β-glucans, mannosylated glycoconjugates, and chitin, a cell wall polysaccharide, are known to provoke immune responses, with chitin showing pro-inflammatory effects. However, the mechanisms involved in chitin recognition by leukocytes are still poorly understood.

Objective:

Thus, this project aims to elucidate the responses of neutrophils in the presence of chitin, as well as to investigate the metabolic pathways involved in this response.

Previous Results:

Human neutrophils produced ROS in response to chitin in a dose-dependent manner. ROS induction by neutrophils was inhibited by the NADPH oxidase inhibitor, DPI, indicating the role of this enzymatic complex in chitin-induced ROS formation. Chitin also induced the formation of NETs. Therefore, our results demonstrate that chitin is a fungal molecular pattern involved in neutrophil activation.

References:

BUETER, Chelsea L.; SPECHT, Charles A.; LEVITZ, Stuart M. Innate sensing of chitin and chitosan. PLoS pathogens, v. 9, n. 1, p. e1003080, 2013.

ISLAM, Md Monirul; TAKEYAMA, Naoshi. Role of neutrophil extracellular traps in health and disease pathophysiology: recent insights and advances. International Journal of Molecular Sciences, v. 24, n. 21, p. 15805, 2023.

BRINKMANN, Volker et al. Neutrophil extracellular traps kill bacteria. science, v. 303, n. 5663, p. 1532-1535, 2004.