Neutrophil killing of Mycobacterium abscessus by intra- and extracellular mechanisms.

Kenneth C Malcolm,Katie R Poch,Jean-Louis Herrmann,Laurent Kremer,Kerstin Pohl,Silvia M Caceres,Jerry A Nick,Audrey Bernut,Donna L Bratton,Nades Palaniyar

doi:10.1371/journal.pone.0196120

Abstract

Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, are increasingly present in soft tissue infections and chronic lung diseases, including cystic fibrosis, and infections are characterized by growth in neutrophil-rich environments. M. abscessus is observed as two distinct smooth and rough morphotypes. The environmental smooth morphotype initiates infection and has a relatively limited ability to activate neutrophils. The rough morphotype has increased virulence and immunogenicity. However, the neutrophil response to the rough morphotype has not been explored. Killing of the smooth and rough strains, including cystic fibrosis clinical isolates, was equivalent. Neutrophil uptake of M. abscessus was similar between morphotypes. Mechanistically, both rough and smooth morphotypes enhanced neutrophil reactive oxygen species generation but inhibition of NADPH oxidase activity did not affect M. abscessus viability. However, inhibition of phagocytosis and extracellular traps reduced killing of the smooth morphotype with lesser effects against the rough morphotype. Neutrophils treated with M. abscessus released a heat-labile mycobactericidal activity against the rough morphotype, but the activity was heat-tolerant against the smooth morphotype. Overall, M. abscessus stimulates ineffective neutrophil reactive oxygen species generation, and key mechanisms differ in killing of the smooth (phagocytosis-dependent, extracellular traps, and heat-tolerant secreted factor) and rough (extracellular traps and a heat-labile secreted factor) morphotypes. These studies represent an essential advancement in understanding the host response to M. abscessus, and help explain the recalcitrance of infection.

Highlights

Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium (NTM) whose incidence of infection has increased over the past decades, especially in patients with chronic lung disease [1,2,3]
Our previous work indicated that neutrophils poorly kill smooth M. abscessus compared to S. aureus [33]
M. abscessus infections are distinguished by neutrophil-rich environments found in soft tissue abscesses and the cystic fibrosis (CF) lung

Summary

Introduction

Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium (NTM) whose incidence of infection has increased over the past decades, especially in patients with chronic lung disease [1,2,3]. The current study addresses the neutrophil bactericidal responses to the smooth and rough morphotypes of M. abscessus to help understand its virulence. These studies indicate distinct and common neutrophil killing mechanisms of M. abscessus morphotypes, and suggest the potential for injurious release of neutrophil products during infection.

Results

Conclusion