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.

Inflammatory macrophage–associated 3-gene signature predicts subclinical allograft injury and graft survival

“…We limited our search to samples run on Affymetrix platforms to ensure platform effect homogeneity. A total of 19 data sets matched our criteria: GSE3982 (47), GSE5099 (48), GSE8668 (49), GSE11292 (50), GSE12453 (51), GSE13987 (52), GSE14879 (53), GSE15743 (54), GSE16020 (55), GSE16836 (56), GSE24759 (57), GSE28490 (58), GSE28491 (58), GSE31773 (59), GSE34515 (60), GSE38043 (34), GSE39889 (35), GSE42519 (36), an dGSE49910 (61). We downloaded all data sets in raw format and normalized each one using gcRMA (62).…”

“…Other groups have investigated intragraft macrophages, though many investigations have focused on murine models of cardiac transplantation (34)(35)(36). Wu et al interrogated macrophage polarization in transplant rejection (35) and found that graft-infiltrating macrophages in a murine model of chronic cardiac transplant rejection demonstrated an M2 (IL-4) phenotype; they reported that blocking the recep- tor P2X7, which may be upregulated in M2 macrophages, improved long-term cardiac allograft survival.…”

“…Wu et al interrogated macrophage polarization in transplant rejection (35) and found that graft-infiltrating macrophages in a murine model of chronic cardiac transplant rejection demonstrated an M2 (IL-4) phenotype; they reported that blocking the recep- tor P2X7, which may be upregulated in M2 macrophages, improved long-term cardiac allograft survival. This group also provided evidence that mTOR deletion both suppresses M2 polarization and may prevent chronic rejection.…”

Social networking of human neutrophils within the immune system

“…3 For example, it has been shown that neutrophils contribute to the development of Lyme arthritis, a chronic inflammatory conditions occurring several months after Borrelia Burgdorferi infection, by recruiting pathogenic Th1/Th17 clones to the inflamed joint. 92 Furthermore, pathogens can evade neutrophil clearance, as recently reported for Neisseria gonorrheae 93 or Mycobacterium abscessus, 94 which were shown to promote their survival by delaying primary granulephagosome fusion 93 or by inducing a limited pattern of neutrophil activation, 94 respectively. Similarly, community-associated methicillinresistant Staphylococcus aureus has been shown to survive within neutrophil phagosome and inhibit macrophage-mediated efferocytosis of community-associated methicillin-resistant S aureus-infected neutrophils.…”

EnhancedIn VitroFormation and Antibiotic Resistance of Nonattached Pseudomonas aeruginosa Aggregates through Incorporation of Neutrophil Products

“…In addition to F-actin and DNA, incorporation of additional neutrophil products likely alters survival properties of P. aeruginosa (55,56). The presence of neutrophils dramatically enhances biofilm mass in the first 24 to 48 h (22)(23)(24)57), the time frame when the planktonic bacteria are generally most vulnerable to eradication by host defenses and antibiotic treatment. The early survival advantage afforded by the presence of dying neutrophils may explain why biofilm-associated P. aeruginosa infection typically occurs in the setting of intense preexisting inflammation, such as burns, wounds, corneal damage, and the CF airway.…”