title: Mycobacterium abscessus induces a limited pattern of neutrophil activation that promotes pathogen survival.
abstract: Mycobacterium abscessus is a rapidly growing mycobacterium increasingly detected in the neutrophil-rich environment of inflamed tissues, including the cystic fibrosis airway. Studies of the immune reaction to M. abscessus have focused primarily on macrophages and epithelial cells, but little is known regarding the neutrophil response despite the predominantly neutrophillic inflammation typical of these infections. In the current study, human neutrophils released less superoxide anion in response to M. abscessus than to Staphylococcus aureus, a pathogen that shares common sites of infection. Exposure to M. abscessus induced neutrophil-specific chemokine and proinflammatory cytokine genes. Although secretion of these protein products was confirmed, the quantity of cytokines released, and both the number and level of gene induction, was reduced compared to S. aureus. Neutrophils mediated killing of M. abscessus, but phagocytosis was reduced when compared to S. aureus, and extracellular DNA was detected in response to both bacteria, consistent with extracellular trap formation. In addition, M. abscessus did not alter cell death compared to unstimulated cells, while S. aureus enhanced necrosis and inhibited apoptosis. However, neutrophils augment M. abscessus biofilm formation. The response of neutrophils to M. abscessus suggests that the mycobacterium exploits neutrophil-rich settings to promote its survival and that the overall neutrophil response was reduced compared to S. aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy.
authors: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America. malcolmk@njhealth.org
authors: Kenneth C
authors: KC
authors: Malcolm
authors: E Michelle
authors: EM
authors: Nichols
authors: Silvia M
authors: SM
authors: Caceres
authors: Jennifer E
authors: JE
authors: Kret
authors: Stacey L
authors: SL
authors: Martiniano
authors: Scott D
authors: SD
authors: Sagel
authors: Edward D
authors: ED
authors: Chan
authors: Lindsay
authors: L
authors: Caverly
authors: George M
authors: GM
authors: Solomon
authors: Paul
authors: P
authors: Reynolds
authors: Donna L
authors: DL
authors: Bratton
authors: Jennifer L
authors: JL
authors: Taylor-Cousar
authors: David P
authors: DP
authors: Nichols
authors: Milene T
authors: MT
authors: Saavedra
authors: Jerry A
authors: JA
authors: Nick
mesh_terms: D018441:Biofilms; D020869:Gene Expression Profiling; D006801:Humans; D009161:Mycobacterium / Q000235:genetics / Q000502:physiology*; D009164:Mycobacterium Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018375:Neutrophil Activation; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides