Promotion of Anti-Tuberculosis Macrophage Activity by L-Arginine in the Absence of Nitric Oxide.
Front Immunol
; 12: 653571, 2021.
Article
in En
| MEDLINE
| ID: mdl-34054815
ABSTRACT
Macrophages are indispensable immune cells tasked at eliminating intracellular pathogens. Mycobacterium tuberculosis (Mtb), one of the most virulent intracellular bacterial pathogens known to man, infects and resides within macrophages. While macrophages can be provoked by extracellular stimuli to inhibit and kill Mtb bacilli, these host defense mechanisms can be blocked by limiting nutritional metabolites, such as amino acids. The amino acid L-arginine has been well described to enhance immune function, especially in the context of driving macrophage nitric oxide (NO) production in mice. In this study, we aimed to establish the necessity of L-arginine on anti-Mtb macrophage function independent of NO. Utilizing an in vitro system, we identified that macrophages relied on NO for only half of their L-arginine-mediated host defenses and this L-arginine-mediated defense in the absence of NO was associated with enhanced macrophage numbers and viability. Additionally, we observed macrophage glycolysis to be driven by both L-arginine and mechanistic target of rapamycin (mTOR), and inhibition of glycolysis or mTOR reduced macrophage control of Mtb as well as macrophage number and viability in the presence of L-arginine. Our data underscore L-arginine as an essential nutrient for macrophage function, not only by fueling anti-mycobacterial NO production, but also as a central regulator of macrophage metabolism and additional host defense mechanisms.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arginine
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Tuberculosis
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Dietary Supplements
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Macrophages
/
Mycobacterium tuberculosis
Limits:
Animals
/
Humans
Language:
En
Journal:
Front Immunol
Year:
2021
Document type:
Article
Affiliation country:
United States
Country of publication:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND