# Characterization of Early Lesions of Human Post-Primary Tuberculosis and Its Progression to Necrosis Using Archival Material of the Pre-Antibiotic Era

## TL;DR

This study examines early post-primary tuberculosis lesions in human lungs from the pre-antibiotic era to understand how the disease progresses to necrosis and how immune responses might be manipulated.

## Contribution

The study characterizes early post-primary TB lesions and their progression using archival human lung tissue and immunohistochemical markers.

## Key findings

- Early post-primary TB lesions show compartmentalized macrophages and T cells with mixed immune phenotypes.
- The PD-L1/PD-1 pathway may help TB evade the immune system during lesion progression.
- MMP-9 and MTB antigens are present in early lesions, suggesting active bacterial involvement.

## Abstract

Primary and post-primary TB are distinct entities. Primary TB occurs when the patient is infected with Mycobacterium tuberculosis (MTB) for the first time without prior immunity, and post-primary TB occurs when the patient has developed immunity against the primary infection. Post-primary TB occurs only in humans. It accounts for 80% of all clinical cases and nearly 100% of transmissions of infection. Early lesions of post-primary TB are reversible, and studying it using modern immunological tools holds the key to developing preventive or treatment strategies. Human lung tissue from untreated TB patients was acquired from pathology archives stored at the Gades Institute of Pathology, Haukeland University Hospital, Bergen, Norway, from 1931 to 1947. Manual immunohistochemistry was performed for macrophage (CD68, CD64 and CD163), T cells (CD3 and CD8), matrix metalloproteinases (MMP-9), and markers for programmed death-pathway PD/PDL-1. Digital quantification was performed using Qupath software. In early lesions of post-primary TB, macrophages showed mixed-phenotype M1 and M2, expressed PDL-1, and were compartmentalized in the alveolar space. T-cells expressed PD-1 and were compartmentalized in the interstitial wall surrounding early lesions. MTB antigens and MMP-9 were also found in early lesions. As the lesion progressed towards necrosis, macrophages showed predominant M1 morphology, and expressions of PDL-1, PD-1, CD8+ cells, and MTB antigens increased. In the early lesions of post-primary TB, the compartmentalization of macrophages in the alveoli and T cells in the interstitium was shown. The PDL-PD1 pathway probably facilitated the mycobacterial growth by evading host immunity.