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

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

Published In Cell Rep, (2018 Nov 13)

Abstract: 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.

PubMed ID: 30428359

MeSH Terms: No MeSH terms associated with this publication