Immunity . . . Li Xiaoxue and others reveal how fruit flies cope with THE accumulation of ROS in the body.

Animals need metabolic and physiological adaptation to maintain homeostasis and cope with environmental stress and bacterial infection by supporting the function of important organs.on the one hand, metabolic adaptation provides energy for corresponding tissues to maintain normal tissue function and promote tissue repair; on the other hand, specific metabolic adaptation also inevitably produces harmful secondary products, leading to tissue damage.this process usually relies on increasing the production of reactive oxygen species (ROS) to promote wound healing or kill invasive microorganisms [1].however, elevated ROS can cause macromolecular damage, cell death and tissue damage.therefore, ROS produced during the immune response must be strictly controlled to avoid harmful effects.at present, several mechanisms of ROS inhibition have been found.for example, Nrf2 transcription factors are activated to increase the expression of antioxidant proteins (such as peroxyredoxin, glutathione peroxidase and catalase), thus controlling ROS concentration to prevent tissue damage.in addition to the above cellular mechanisms, little is known about how organisms respond to ROS toxicity at the body level.recently, Bruno Lemaitre of EPFL, Switzerland, and the team of Li Xiaoxue (Li Xiaoxue is the corresponding author and the first author) published an article in the journal immunity, namely, the accumulation of ROS induced inflammatory oxidized lipids and protection drophila from tissue Damage, we found that Drosophila could eliminate lipids in haemolymph through martrazzi, a lipid binding protein, in order to avoid ROS induced damage.in this paper, the authors used Drosophila melanogaster as a model, and found that pathogen infection or tissue damage could lead to the excretion of lipids from haemolymph (insect blood) by the Malpighian tubules (insect kidney).this lipid clearance is mediated by the stress-induced lipid binding protein matrazzi.the gene is highly enriched in the Malpighian tubules and responds to a variety of environmental pressures, including systemic infection, intestinal infection, system damage and high salt stress.the Drosophila lacking matrazzi had higher concentration of ROS and accumulated a large amount of malondialdehyde (MDA).ROS in haemolymph also causes damage to other tissues of Drosophila melanogaster. For example, the excretion function of Mahalanobis tube is greatly affected, and the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE) appears at the same time.these results lead to the fact that flies lacking matrazzi are more likely to die of infection, tissue damage and environmental stress.this indicates that matrazzi's main function is to protect the organism from ROS damage caused by pathogen infection or tissue damage.human kidney is a highly active organ of metabolism, so it is vulnerable to the influence of redox imbalance. it is generally believed that oxidative stress can lead to the development of kidney diseases, such as acute kidney injury and chronic kidney disease. patients with chronic kidney disease show increased superoxide and oxidized low-density lipoprotein, and decreased antioxidant activity. in addition, the lipid peroxidation product MDA has not only been proved to be a marker of chronic kidney disease, but also can induce dysfunctional high density lipoprotein (HDL). patients with renal insufficiency also have the characteristic lipid pattern of hypertriglyceridemia. our findings suggest that clearance of hemolymph lipids contributes to physiological adaptation to protect the host kidney from excessive ROS during immune and stress responses. although no specific homologous gene has been found in mammalian system, the discovery provides a possible link between renal function and blood lipid content outside insect system. Lambeth, J.D., and Neish, A.S. (2014). NOx enzymes and new thinking on reactive oxygen: a double edged sword revised. Annu Rev.Pathol . 9, 119–145.