title: Outbreaks of Mycobacterium tuberculosis MDR strains differentially induce neutrophil respiratory burst involving lipid rafts, p38 MAPK and Syk.
abstract: BACKGROUND
  Neutrophils (PMN) are the first cells to infiltrate the lung after infection, and they play a significant protective role in the elimination of pathogen, by releasing preformed oxidants and proteolytic enzymes from granules and generating ROS, thus limiting inflammation by succumbing to apoptosis. In a previous study, we found marked differences in ROS-induced apoptosis between two Mycobacterium tuberculosis (Mtb) strains, M and Ra, representative of widespread Mtb families in South America, i.e. Haarlem and Latin-American Mediterranean (LAM), being strain M able to generate further drug resistance and to disseminate aggressively.
  
  
  METHODS
  In this study we evaluate the nature of bacteria-PMN interaction by assessing ROS production, apoptosis, lipid raft coalescence, and phagocytosis induced by Mtb strains.
  
  
  RESULTS
  Dectin-1 and TLR2 participate in Mtb-induced ROS generation and apoptosis in PMN involving p38 MAPK and Syk activation with the participation of a TLR2-dependent coalescence of lipid rafts. Further, ROS production occurs during the phagocytosis of non-opsonized bacteria and involves α-glucans on the capsule. In contrast, strain M lacks the ability to induce ROS because of: 1) a reduced phagocytosis and 2) a failure in coalescence of lipid raft.
  
  
  CONCLUSIONS
  The differences in wall composition could explain the success of some strains which stay unnoticed by the host through inhibition of apoptosis and ROS but making possible its replication inside PMN as a potential evasion mechanism. Innate immune responses elicited by Mtb strain-to-strain variations need to be considered in TB vaccine development.
authors.forename: María Mercedes
authors.initials: MM
authors.lastname: Romero
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Basile
authors.forename: Beatriz
authors.initials: B
authors.lastname: López
authors.forename: Viviana
authors.initials: V
authors.lastname: Ritacco
authors.forename: Lucía
authors.initials: L
authors.lastname: Barrera
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Sasiain
authors.affiliation: Inmunologia de enfermedades respiratorias, IMEX-CONTICET-ANM, Buenos Aires, Argentina. melealeman@hotmail.com.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alemán
mesh_terms: D017209:Apoptosis / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000378:metabolism; D005936:Glucans / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000378:metabolism*; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D005677:G(M1) Ganglioside; D005936:Glucans; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D017382:Reactive Oxygen Species; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2; D048051:p38 Mitogen-Activated Protein Kinases; D000099181:Dectin-1; C508606:CXCL8 protein, human; C495342:TLR2 protein, human; C000606896:SYK protein, human