Heightened Systemic Levels of Neutrophil and Eosinophil Granular Proteins in Pulmonary Tuberculosis and Reversal following Treatment

Infect Immun. 2018 May 22;86(6):e00008-18. doi: 10.1128/IAI.00008-18. Print 2018 Jun.

Abstract

Granulocytes are activated during Mycobacterium tuberculosis infection and act as immune effector cells, and granulocyte responses are implicated in tuberculosis (TB) pathogenesis. Plasma levels of neutrophil and eosinophil granular proteins provide an indirect measure of degranulation. In this study, we wanted to examine the levels of neutrophil and eosinophil granular proteins in individuals with pulmonary tuberculosis (PTB) and to compare them with the levels in individuals with latent TB (LTB). Hence, we measured the plasma levels of myeloperoxidase (MPO), neutrophil elastase, proteinase 3, major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPX) in these individuals. Finally, we also measured the levels of all of these proteins in PTB individuals following antituberculosis treatment (ATT). Our data reveal that PTB individuals are characterized by significantly higher plasma levels of MPO, elastase, proteinase 3, as well as MBP and EDN in comparison to those in LTB individuals. Our data also reveal that ATT resulted in the reversal of all of these changes, indicating an association with TB disease. Finally, our data show that the systemic levels of MPO and proteinase 3 can significantly discriminate PTB from LTB individuals. Thus, our data suggest that neutrophil and eosinophil granular proteins could play a potential role in the innate immune response and, therefore, the pathogenesis of pulmonary TB.

Keywords: eosinophils; granular proteins; neutrophils; tuberculosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antitubercular Agents / therapeutic use*
  • Eosinophil Cationic Protein / blood
  • Eosinophil Cationic Protein / metabolism
  • Eosinophil Major Basic Protein / blood
  • Eosinophil Major Basic Protein / metabolism
  • Eosinophil Peroxidase / blood
  • Eosinophil Peroxidase / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Latent Tuberculosis / blood*
  • Latent Tuberculosis / drug therapy*
  • Leukocyte Elastase / blood*
  • Leukocyte Elastase / metabolism
  • Male
  • Middle Aged
  • Myeloblastin / blood
  • Myeloblastin / metabolism
  • Peroxidase / blood
  • Peroxidase / metabolism
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / drug therapy*
  • Young Adult

Substances

  • Antitubercular Agents
  • Eosinophil Peroxidase
  • Peroxidase
  • Eosinophil Cationic Protein
  • Eosinophil Major Basic Protein
  • RNASE3 protein, human
  • Leukocyte Elastase
  • Myeloblastin