Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis
Authors: Jeremie M Lever
Alasdair Leslie
Gordon Wells
Gene P Siegal
Ryan M Wells
Amie Traylor
Shepherd Nhamoyebonde
Adrie J C Steyn
Anupam Agarwal
James F George
Joel N Glasgow
Veena B Antony
Pratistadevi K Ramdial
Rajhmun Madansein
Krishna C Chinta
Kievershen Nargan
Vineel P Reddy
Vikram Saini
Jessy Deshane
Md Aejazur Rahman
Journal: Cell reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: free radical; heme oxygenase-1; histopathological spectrum; human TB pathology; human pulmonary tuberculosis
Affiliations: Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Africa Health Research Institute, Durban 4001, South Africa., Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Inkosi Albert Luthuli Central Hospital, Durban 4041, South Africa., Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Division of Cardiothoracic Surgery, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Department of Anatomical Pathology, NHLS, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban 4091, South Africa., Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Veterans Affairs, Birmingham, AL 35294, USA., Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Africa Health Research Institute, Durban 4001, South Africa; UAB Center for AIDS Research, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Center for Free Radical Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: .

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. 

Retracted: No

PubPeer comments:
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 #1 Thanks for pointing this out to us. This issue has been corrected, see below. Regards, Adrie Erratum for: Cell Rep. 2019 Sep 17;28(12):3286. doi: 10.1016 j.celrep.2019.08.081. Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis. Chinta KC, Rahman MA, Saini V, Glasgow JN, Reddy VP, Lever JM, Nhamoyebonde S, Leslie A, Wells RM, Traylor A, Madansein R, Siegal GP, Antony VB, Deshane J, Wells G, Nargan K, George JF, Ramdial PK, Agarwal A, Steyn AJC. ,