Activation of macrophages mediates dietary restriction-induced splenic involution

Malnutrition affects various physiological functions, including immune defenses. However, it remains unclear how malnutrition reduces immune responses.

To elucidate mechanisms underlying malnutrition-induced immunodeficiency, we focused on the spleen, which plays an essential role in the immune system, and examined the impacts of malnutrition on the spleen.

The impact of malnutrition on the spleen was assessed using dietary-restricted mice as a model. Weights of the spleen were measured and normalized to body weights. Macrophage maker protein expression was observed using fluorescent immunostaining. Clodronate-containing liposomes were injected into the mice to test whether macrophages are involved in splenic changes induced by dietary restriction.

The spleen of dietary-restricted mice involuted with significant reductions in the relative weight of the spleen to the body weight and ratio of the red pulp in the spleen. Then, we examined whether macrophages mediate dietary restriction-induced splenic involution. The IBA1/AIF1 protein level was increased in the marginal zone, which is the interface between the red and white pulps of the spleen, by dietary restriction. We tested whether macrophages are needed for dietary restriction-induced splenic involution. The increase in IBA1/AIF1 expression in the marginal zone and splenic involution were suppressed by clodronate liposome administration. These results indicate that the macrophages in the splenic marginal zone were activated by dietary restriction and were required for dietary restriction-induced splenic involution.

Our study proposes macrophage-mediated splenic involution as a novel mechanism linking malnutrition to immunodeficiency.