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

Academic Article

Abstract

  • © 2018 The Author(s) 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.
  • Published In

  • Cell Reports  Journal
  • Digital Object Identifier (doi)

    Author List

  • Chinta KC; Rahman MA; Saini V; Glasgow JN; Reddy VP; Lever JM; Nhamoyebonde S; Leslie A; Wells RM; Traylor A
  • Start Page

  • 1938
  • End Page

  • 1952.e5
  • Volume

  • 25
  • Issue

  • 7