Effect of acute nutritional deprivation on immune function in mice. I. Macrophages
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Abstract:
This study was designed to explore the effects of acute nutritional deprivation (starvation) on macrophage function in mice. In vivo macrophage activity was increased by starvation, as determined by multiplication of Listeria monocytogenes in both spleens and livers after intravenous injection. Similarly, in vitro studies revealed that the capacity of peritoneal macrophages to kill listeria was enhanced by starvation. This function was increased further by the addition of small concentrations of lipopolysaccharide (LPS; 10-100 ng/ml). The bactericidal activity of macrophages from starved mice, however, did not reach the levels observed with macrophages from BCG-infected mice. Furthermore, LPS did not appear to be an important second signal for macrophage activation in vivo, as LPS-unresponsive mice (C3H/HeJ and A/J) were protected by starvation. In contrast to these results we found that starved mice were not protected against Toxoplasma gondii infection and that macrophages from starved mice were unable to prevent multiplication of toxoplasma trophozoites in vitro. In toto, these experiments suggest that macrophage function is enhanced by starvation, but that this enhancement is not sufficient to fulfill all criteria for macrophage activation.
Insights
Starvation boosts macrophage activity against Listeria monocytogenes in mice, enhancing their ability to kill bacteria. However, this starvation-induced enhancement is insufficient for protection against Toxoplasma gondii.
Area of Science:
- Immunology
- Nutritional Science
- Microbiology
Background:
- Macrophage function is critical for host defense against microbial infections.
- Nutritional status can significantly impact immune cell activity.
- Understanding how nutritional deprivation affects macrophages is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the impact of acute nutritional deprivation (starvation) on macrophage function in mice.
- To determine if starvation enhances macrophage bactericidal activity in vivo and in vitro.
- To assess the role of lipopolysaccharide (LPS) as a second signal in starvation-induced macrophage activation.
Main Methods:
- In vivo studies involved intravenous injection of Listeria monocytogenes into starved and control mice.
- In vitro studies assessed the capacity of peritoneal macrophages from starved mice to kill Listeria and Toxoplasma.
- Experiments utilized LPS-unresponsive mouse models (C3H/HeJ and A/J) to evaluate LPS's role in vivo.
Main Results:
- Starvation increased macrophage activity in vivo, evidenced by enhanced control of Listeria monocytogenes replication in spleens and livers.
- In vitro, macrophages from starved mice exhibited enhanced killing of Listeria, further augmented by low concentrations of LPS.
- Despite enhanced bactericidal activity against Listeria, starved mice were not protected against Toxoplasma gondii, and their macrophages failed to inhibit T. gondii multiplication in vitro.
Conclusions:
- Acute starvation enhances macrophage function, particularly against certain bacterial infections like Listeria.
- Lipopolysaccharide (LPS) is not essential for starvation-induced protection in vivo.
- Starvation-induced macrophage enhancement is specific and does not confer broad protection against all pathogens, failing to meet all criteria for full macrophage activation.