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

Publication date: 13 November 2018Source: Cell Reports, Volume 25, Issue 7Author(s): 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. SteynSummaryHeme 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 immun...
Source: Cell Reports - Category: Cytology Source Type: research