Cell Reports (Nov 2018)

Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis

  • Krishna C. Chinta,
  • Md. Aejazur Rahman,
  • Vikram Saini,
  • Joel N. Glasgow,
  • Vineel P. Reddy,
  • Jeremie M. Lever,
  • Shepherd Nhamoyebonde,
  • Alasdair Leslie,
  • Ryan M. Wells,
  • Amie Traylor,
  • Rajhmun Madansein,
  • Gene P. Siegal,
  • Veena B. Antony,
  • Jessy Deshane,
  • Gordon Wells,
  • Kievershen Nargan,
  • James F. George,
  • Pratistadevi K. Ramdial,
  • Anupam Agarwal,
  • Adrie J.C. Steyn

Journal volume & issue
Vol. 25, no. 7
pp. 1938 – 1952.e5

Abstract

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Summary: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammatory responses and redox homeostasis; however, its role during pulmonary tuberculosis (TB) remains unclear. Using freshly resected human TB lung tissue, we examined the role of HO-1 within the cellular and pathological spectrum of TB. Flow cytometry and histopathological analysis of human TB lung tissues showed that HO-1 is expressed primarily in myeloid cells and that HO-1 levels in these cells were directly proportional to cytoprotection. HO-1 mitigates TB pathophysiology by diminishing myeloid cell-mediated oxidative damage caused by reactive oxygen and/or nitrogen intermediates, which control granulocytic karyorrhexis to generate a zonal HO-1 response. Using whole-body or myeloid-specific HO-1-deficient mice, we demonstrate that HO-1 is required to control myeloid cell infiltration and inflammation to protect against TB progression. Overall, this study reveals that zonation of HO-1 in myeloid cells modulates free-radical-mediated stress, which regulates human TB immunopathology. : Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammation and redox homeostasis; however, its role in tuberculosis (TB) is unclear. Using freshly resected human lung tissue and HO-1-deficient mice, Chinta et al. demonstrate that HO-1 in myeloid cells is important for controlling inflammatory and free-radical-mediated tissue damage in TB. Keywords: mycobacterium tuberculosis, heme oxygenase-1, human pulmonary tuberculosis, histopathological spectrum, human TB pathology, myeloid cell inflammation, macrophage, neutrophil, karyorrhexis, free radical