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Updated: May 23, 2026
An Experimental Model to Study Tuberculosis-Malaria Coinfection upon Natural Transmission of Mycobacterium tuberculosis and Plasmodium berghei
Published on: February 17, 2014
Uptake and accumulation of oxidized low-density lipoprotein during Mycobacterium tuberculosis infection in guinea
Gopinath S Palanisamy1, Natalie M Kirk, David F Ackart
1Department of Microbiology, Colorado State University, Fort Collins, Colorado, United States of America.
Abstract:
The typical host response to infection of humans and some animals by M. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. In previous studies we showed that infection of immunologically naïve guinea pigs with M. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondialdehyde, a bi-product of lipid peroxidation. Here we show that in addition, the generation of excessive reactive oxygen species in vivo resulted in the accumulation of oxidized low density lipoproteins (OxLDL) in pulmonary and extrapulmonary granulomas, serum and lung macrophages collected by bronchoalveolar lavage. Macrophages from immunologically naïve guinea pigs infected with M. tuberculosis also had increased surface expression of the type 1 scavenger receptors CD36 and LOX1, which facilitate the uptake of oxidized host macromolecules including OxLDL. Vaccination of guinea pigs with Bacillus Calmette Guerin (BCG) prior to aerosol challenge reduced the bacterial burden as well as the intracellular accumulation of OxLDL and the expression of macrophage CD36 and LOX1. In vitro loading of guinea pig lung macrophages with OxLDL resulted in enhanced replication of bacilli compared to macrophages loaded with non-oxidized LDL. Overall, this study provides additional evidence of oxidative stress in M. tuberculosis infected guinea pigs and the potential role OxLDL laden macrophages have in supporting intracellular bacilli survival and persistence.
Insights
Tuberculosis infection causes oxidative stress, leading to oxidized LDL accumulation in macrophages. This supports bacterial survival, but BCG vaccination reduces these effects.
Area of Science:
- Immunology
- Microbiology
- Oxidative Stress Research
Background:
- Tuberculosis (TB) infection typically involves inflammatory cells and granuloma formation with caseous necrosis.
- Previous studies demonstrated localized/systemic oxidative stress in TB-infected guinea pigs, depleting antioxidant capacity and increasing malondialdehyde.
Purpose of the Study:
- To investigate the role of excessive reactive oxygen species (ROS) in the accumulation of oxidized low-density lipoproteins (OxLDL) during M. tuberculosis infection.
- To examine the impact of OxLDL on macrophage scavenger receptor expression and its implications for M. tuberculosis survival.
- To evaluate the effect of Bacillus Calmette-Guérin (BCG) vaccination on OxLDL accumulation and M. tuberculosis burden.
Main Methods:
- Quantified OxLDL accumulation in granulomas, serum, and bronchoalveolar lavage (BAL) macrophages from M. tuberculosis-infected guinea pigs.
- Assessed surface expression of scavenger receptors CD36 and LOX1 on macrophages.
- Investigated the effect of BCG vaccination on bacterial burden, OxLDL, and scavenger receptor expression.
- Performed in vitro experiments loading guinea pig lung macrophages with OxLDL to assess M. tuberculosis replication.
Main Results:
- Excessive ROS generation in vivo led to OxLDL accumulation in pulmonary/extrapulmonary granulomas, serum, and BAL macrophages.
- Infected macrophages showed increased surface expression of CD36 and LOX1, facilitating OxLDL uptake.
- BCG vaccination reduced bacterial burden, intracellular OxLDL, and macrophage CD36/LOX1 expression.
- In vitro OxLDL loading enhanced M. tuberculosis replication within macrophages.
Conclusions:
- This study provides further evidence of oxidative stress in M. tuberculosis infection.
- Oxidized LDL-laden macrophages may play a crucial role in supporting intracellular M. tuberculosis survival and persistence.
- BCG vaccination demonstrates a potential to mitigate oxidative stress-induced pathways that favor M. tuberculosis persistence.
