Related Experiment Video
Updated: May 20, 2026
Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Macrophages from elders are more permissive to intracellular multiplication of Mycobacterium tuberculosis
José M Guerra-Laso1, Sandra González-García, Carolina González-Cortés
1Servicio de Medicina Interna, Hospital de León, Altos de Nava s/n, 24008, León, Spain.
Abstract:
The elderly account for a disproportionate share of all tuberculosis cases, and the population ageing may not fully explain this phenomenon. We have performed in vitro infection experiments to investigate whether there is an immunological basis for the apparent susceptibility of elders to tuberculosis. In our infection model, Mycobacterium tuberculosis induces a higher production of interleukin (IL)-6 and reactive oxygen species in macrophages from elders than from younger adults. This response did not prevent, however, an increased multiplication of M. tuberculosis in macrophages from elders as compared with the growth observed within cells from adults. By performing a factorial experiment, we have found that IFN-γ, but not IL-1β, IL-6 or TNF-α, stimulate the macrophages to restrict the multiplication of the bacterium in macrophages from elders. Although monocytes from elders seem to be in a higher level of activation, we present evidences that protein tyrosine phosphorylation response induced by M. tuberculosis is stronger in monocytes from adults than from elders. Using a protein array that detects 71 tyrosine phosphorylated kinases, we identified Pyk2 as the only kinase that displayed a difference of intensity larger than 50 % in adults than in elders. Furthermore, monocytes from elders that were incubated in the presence of tyrosine kinase inhibitors (genistein and PP2) allowed a higher level of bacterial multiplication. These observations may help to explain the susceptibility of elders to tuberculosis. An unexpected result was that both genistein and its negative control, daidzein, abundant soy isoflavones, promoted intracellular mycobacterial growth.
Insights
Elderly individuals are more susceptible to tuberculosis due to impaired immune responses in macrophages. Interferon-gamma (IFN-γ) shows potential in restricting mycobacterium tuberculosis growth in elders.
Area of Science:
- Immunology
- Infectious Diseases
- Gerontology
Background:
- Tuberculosis (TB) disproportionately affects the elderly, with population aging alone not fully explaining this trend.
- Investigating the immunological basis for increased TB susceptibility in older adults is crucial.
Purpose of the Study:
- To investigate the immunological factors contributing to the heightened susceptibility of the elderly to tuberculosis (TB).
- To identify potential therapeutic targets for TB in older populations.
Main Methods:
- In vitro infection experiments using macrophages from elderly and younger adults.
- Measurement of cytokine production (IL-6, IL-1β, TNF-α) and reactive oxygen species.
- Assessment of Mycobacterium tuberculosis growth within macrophages.
- Factorial experiment to evaluate the role of interferons (IFN-γ).
- Analysis of protein tyrosine phosphorylation and kinase activity (Pyk2) using protein arrays.
- Treatment with tyrosine kinase inhibitors (genistein, PP2).
Main Results:
- Macrophages from elders produced more IL-6 and reactive oxygen species but supported increased M. tuberculosis multiplication.
- IFN-γ, but not other tested cytokines, restricted bacterial growth in elder macrophages.
- Protein tyrosine phosphorylation response to M. tuberculosis was weaker in elders, with Pyk2 showing significantly lower activity.
- Tyrosine kinase inhibitors enhanced bacterial growth in elder monocytes.
- Soy isoflavones (genistein, daidzein) unexpectedly promoted intracellular mycobacterial growth.
Conclusions:
- Impaired protein tyrosine phosphorylation and altered cytokine responses in elder macrophages contribute to TB susceptibility.
- IFN-γ may play a role in controlling M. tuberculosis in the elderly.
- Targeting tyrosine kinases could be a potential therapeutic strategy, but caution is needed with compounds like genistein.
Related Concept Videos
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:28Pulmonary Tuberculosis II
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...