Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-directed Therapies

Version 1 : Received: 17 July 2021 / Approved: 19 July 2021 / Online: 19 July 2021 (11:02:57 CEST)
Version 2 : Received: 28 September 2021 / Approved: 29 September 2021 / Online: 29 September 2021 (09:56:22 CEST)

A peer-reviewed article of this Preprint also exists.

Brown, R.E.; Hunter, R.L. Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies. Pathogens 2021, 10, 1572. Brown, R.E.; Hunter, R.L. Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies. Pathogens 2021, 10, 1572.

Journal reference: Pathogens 2021, 10, 1572
DOI: 10.3390/pathogens10121572

Abstract

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Keywords

tuberculosis; secretory antigens; bronchiolar epithelium; alveolar pneumocytes; M2 polarization; COX-2, FAS; Pathogenesis; early lesion

Subject

MEDICINE & PHARMACOLOGY, Pathology & Pathobiology

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