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
Affiliations
Krishna C. Chinta
Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Md. Aejazur Rahman
Africa Health Research Institute, Durban 4001, South Africa
Vikram Saini
Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Joel N. Glasgow
Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Vineel P. Reddy
Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jeremie M. Lever
Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Shepherd Nhamoyebonde
Africa Health Research Institute, Durban 4001, South Africa
Alasdair Leslie
Africa Health Research Institute, Durban 4001, South Africa
Ryan M. Wells
Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Amie Traylor
Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Rajhmun Madansein
Inkosi Albert Luthuli Central Hospital, Durban 4041, South Africa
Gene P. Siegal
Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Veena B. Antony
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jessy Deshane
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Gordon Wells
Africa Health Research Institute, Durban 4001, South Africa
Kievershen Nargan
Africa Health Research Institute, Durban 4001, South Africa
James F. George
Division of Cardiothoracic Surgery, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Pratistadevi K. Ramdial
Department of Anatomical Pathology, NHLS, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban 4091, South Africa
Anupam Agarwal
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
Adrie J.C. Steyn
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; Corresponding author
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
