Neutrophil kinetics of Shigella infection in Macaca mulatta (Rhesus macaques).

INTRODUCTION

Neutrophil migration is a hallmark of acute inflammation and represents a key component of the early innate immune response to bacterial infection. We previously demonstrated the ability to track neutrophil movement from bone marrow to blood and subsequently to tissues using 5-bromo-2'-deoxyuridine (BrdU) pulse labeling in healthy adult rhesus macaques (Macaca mulatta), observing a consistent pattern of neutrophil kinetics during homeostasis.

METHODS

In this study, we extend our analyses to investigate the kinetics of neutrophil movement during acute inflammatory responses using Shigella sonnei, the causative agent of bacillary dysentery, as a model for acute bacterial infection. Twelve adult rhesus macaques were divided into three groups and challenged with varying doses of S. sonnei via gastric-oral lavage.

RESULTS

BrdU labeling revealed significant neutrophil consumption from blood into tissues and replenishment from bone marrow to blood as early as three days post-challenge, with a transient increase in neutrophil counts in blood at day nine post-challenge. Moreover, the extent of neutrophil kinetic changes correlated with the doses of S. sonnei.

DISCUSSION: These findings suggest that BrdU-labeled neutrophil kinetics provide valuable insights into neutrophil dynamics in vivo. This knowledge can be crucial for future studies that monitor acute inflammatory responses to infectious agents using nonhuman primate models. Additionally, it may aid in understanding the mechanisms of disease development and in creating effective intervention strategies.