Human neutrophils phagocytose and kill Acinetobacter baumannii and A. pittii

Abstract

Acinetobacter baumannii is a common cause of health care associated infections worldwide. A. pittii is an opportunistic pathogen also frequently isolated from Acinetobacter infections other than those from A. baumannii. Knowledge of Acinetobacter virulence factors and their role in pathogenesis is scarce. Also, there are no detailed published reports on the interactions between A. pittii and human phagocytic cells. Using confocal laser and scanning electron microscopy, immunofluorescence, and live-cell imaging, our study shows that immediately after bacteria-cell contact, neutrophils rapidly and continuously engulf and kill bacteria during at least 4 hours of infection in vitro. After 3 h of infection, neutrophils start to release neutrophil extracellular traps (NETs) against Acinetobacter. DNA in NETs colocalizes well with human histone H3 and with the specific neutrophil elastase. We have observed that human neutrophils use large filopodia as cellular tentacles to sense local environment but also to detect and retain bacteria during phagocytosis. Furthermore, co-cultivation of neutrophils with human differentiated macrophages before infections shows that human neutrophils, but not macrophages, are key immune cells to control Acinetobacter. Although macrophages were largely activated by both bacterial species, they lack the phagocytic activity demonstrated by neutrophils.

Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

“…It appears that A. baumannii is not recognized as a foreign body that stimulates a strong inflammatory response by neutrophils. However, this is clearly in contrast to the findings of other ( 39 ). Lazaro-Diez et al showed that A. baumannii is indeed phagocytosed by neutrophils and induces NET formation.…”

Mechanisms Protecting Acinetobacter baumannii against Multiple Stresses Triggered by the Host Immune Response, Antibiotics and Outside-Host Environment

“…The role of macrophages in eliminating A. baumannii remains controversial. Most studies showed that macrophages play a minor role during A. baumannii infection [ 14 , 15 , 21 ]. However, Qiu et al demonstrated that macrophages could be the first line of defense against respiratory A. baumannii infections; the depletion of alveolar macrophages significantly enhanced the susceptibility of mice to A. baumannii [ 22 ].…”

Role of immunodeficiency in Acinetobacter baumannii associated pneumonia in mice

“…Early recruitment of neutrophils which take responsibilities in rapidly and continuously engulfing and killing bacteria is critical for initiating an efficient host defense against respiratory A. baumannii infection. [ 23 , 24 ] It was found that neutropenia was related to inhibited bacteria clearance, alteration of pro-inflammatory cytokine release thus leading to more severe microbial disease in A. baumannii infection. [ 25 , 26 ] In our study, at 6 h of A. baumannii administration, the recruitment of peripheral neutrophils sharply rose in mice with normal immunity.…”