AI Article Synopsis

  • * Researchers induced nonreplication in M. tuberculosis through nutrient starvation, which led to higher bacterial loads and more severe lung damage in infected mice after several weeks compared to those infected with actively growing bacteria.
  • * The immune response shifted from a strong T cell response characterized by multiple cytokines to a weaker response dominated by IFN-γ alone, suggesting that the nonreplicating form may evade immune defenses and enhance disease progression and transmission.

Article Abstract

When infected with Mycobacterium tuberculosis, most individuals will remain clinically healthy but latently infected. Latent infection has been proposed to partially involve M. tuberculosis in a nonreplicating stage, which therefore represents an M. tuberculosis phenotype that the immune system most likely will encounter during latency. It is therefore relevant to examine how this particular nonreplicating form of M. tuberculosis interacts with the host immune system. To study this, we first induced a state of nonreplication through prolonged nutrient starvation of M. tuberculosis in vitro. This resulted in nonreplicating persistence even after prolonged culture in phosphate-buffered saline. Infection with either exponentially growing M. tuberculosis or nutrient-starved M. tuberculosis resulted in similar lung CFU levels in the first phase of the infection. However, between week 3 and 6 postinfection, there was a very pronounced increase in bacterial levels and associated lung pathology in nutrient-starved-M. tuberculosis-infected mice. This was associated with a shift from CD4 T cells that coexpressed gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) or IFN-γ, TNF-α, and interleukin-2 to T cells that only expressed IFN-γ. Thus, nonreplicating M. tuberculosis induced through nutrient starvation promotes a bacterial form that is genetically identical to exponentially growing M. tuberculosis yet characterized by a differential impact on the immune system that may be involved in undermining host antimycobacterial immunity and facilitate increased pathology and transmission.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645392PMC
http://dx.doi.org/10.1128/IAI.01055-15DOI Listing

Publication Analysis

Top Keywords

immune system
12
tuberculosis
11
mycobacterium tuberculosis
8
nutrient starvation
8
exponentially growing
8
growing tuberculosis
8
differential influence
4
influence nutrient-starved
4
nutrient-starved mycobacterium
4
tuberculosis adaptive
4

Similar Publications

Prospects for potential therapy targeting immune‑associated factors in endometriosis (Review).

Mol Med Rep

March 2025

Key Laboratory for Experimental Teratology of Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China.

Endometriosis (EM) is a chronic inflammatory disease that is one of the most common causes of gynecological systemic lesions in women before menopause. The most representative histological feature of EM is that the endometrium appears outside of the uterine cavity, often in the ovary. Although it is generally accepted that the epithelial and stromal cells of the ectopic endometrium are not malignant, they still have numerous similarities to malignant tumors, including considerable changes to the immune microenvironment (immune monitoring disorder), the creation of a specific hormone environment, high levels of oxidative stress, chronic inflammation and abnormal immune cell regulation.

View Article and Find Full Text PDF

Psoriasis is a multifactorial immune-mediated inflammatory disease. Its pathogenesis involves abnormal accumulation of neutrophils and T-cell-related abnormalities. Pyroptosis is a type of regulated cell death associated with innate immunity, but its role in psoriasis is unclear.

View Article and Find Full Text PDF

Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults.

Front Immunol

December 2024

Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.

Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8 T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults.

View Article and Find Full Text PDF

CD8 T cell exhaustion in the tumor microenvironment of breast cancer.

Front Immunol

December 2024

Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians University, Munich, Germany.

CD8+ T cells are crucial cytotoxic components of the tumor immune system. In chronic inflammation, they become low-responsive, a state known as T cell exhaustion (TEX). The aim of immune checkpoint blockade is to counteract TEX, yet its dynamics in breast cancer remain poorly understood.

View Article and Find Full Text PDF

Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy Tumor Reactive T cell (TRT) Process has been developed.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: