Immunosuppressive Features of the Microenvironment in Lymph Nodes Granulomas from Tuberculosis and HIV-Co-Infected Patients.

Abstract

Tuberculosis (TB) and HIV co-infection claims many lives every year. This study assessed immune responses in Mycobacterium tuberculosis-infected lymph node tissues from HIV-negative and HIV-positive patients compared with the peripheral circulation with a focus on myeloid cells and the cell-signaling enzymes, inducible nitric oxide synthase, and arginase (Arg)-1. Methods included immunohistochemistry or confocal microscopy and computerized image analyses, quantitative real-time PCR, multiplex Luminex, and flow cytometry. These findings indicate enhanced chronic inflammation and immune activation in TB/HIV co-infection but also enhanced immunosuppressive responses. Poorly formed necrotic TB granulomas with a high expression of M. tuberculosis antigens were elevated in TB/HIV-co-infected lymph nodes, and inducible nitric oxide synthase and Arg-1 expression was significantly higher in TB/HIV-co-infected compared with HIV-negative TB or control tissues. High Arg-1 expression was found in myeloid cells with a phenotype characteristic of myeloid-derived suppressor cells (MDCS) that were particularly abundant in TB/HIV-co-infected tissues. Accordingly, Lin-/HLA-DRlow/int/CD33+/CD11b+/CD15+ granulocytic myeloid-derived suppressor cells were significantly elevated in blood samples from TB/HIV-co-infected patients. CD15+ myeloid-derived suppressor cells correlated with plasma HIV viral load and M. tuberculosis antigen load in tissue but were inversely associated with peripheral CD4 T-cells counts. Enhanced chronic inflammation driven by M. tuberculosis and HIV co-infection may promote Arg-1-expressing MDSCs at the site of infection thereby advancing TB disease progression.

• Authors: Senait Ashenafi, Jagadeeswara Rao Muvva, Akhirunnesa Mily, Johanna Snäll, Martha Zewdie, Menberework Chanyalew, Anders Rehn, Sayma Rahman, Getachew Aseffa, Amsalu Bekele, Getachew Aderaye, Beede Lema, Mattias Svensson, Susanna Brighenti
• Journal: The American journal of pathology (Am J Pathol) Vol. 192 Issue 4 Pg. 653-670 (04 2022) ISSN: 1525-2191 [Electronic] United States
• PMID: 35092727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Nitric Oxide Synthase Type II

Topics

• Coinfection
• Granuloma
• HIV Infections (complications)
• Humans
• Inflammation
• Lymph Nodes (metabolism)
• Mycobacterium tuberculosis
• Nitric Oxide Synthase Type II (metabolism)
• Tuberculosis (complications)