Petrignani, B. | bioRxiv Science

bioRxiv2025

The secreted Nimrod NimB1 negatively regulates early steps of apoptotic cell phagocytosis in Drosophila

Efferocytosis, the efficient clearance of apoptotic cells (ACs) by phagocytes, is vital for maintaining tissue homeostasis. Here, we reveal the role of the secreted protein NimB1 in reducing apoptotic cell recognition and binding in the early stages of efferocytosis. NimB1 is expressed in macrophages (also called plasmatocytes) and binds to ACs in a phosphatidylserine-dependent manner. Structural analysis shows that NimB1 shares striking similarities with the bridging molecule NimB4, and possesses two phosphatidylserine-binding motifs, supporting its role in efferocytosis. Larval macrophages of NimB1 null mutants display a hyper-phagocytic phenotype characterized by increased engulfment of ACs. Confocal imaging reveals that NimB1 specifically inhibits early steps in internalization of ACs, but does not impact phagosome maturation. We find that NimB1 is a secreted factor that negatively regulates efferocytosis, antagonizing the role of NimB4. Our study and the analogous opposing roles of Draper Isoforms II and I in efferocytosis suggest that a balance of negative and positive regulators allows optimization of the rate of apoptotic cell clearance by macrophages.

immunology↗

bioRxiv2019

Metabolic adjustment of Drosophila hemocyte number and sessility by an adipokine

In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that the adipokine NimB5 is produced in the fat body upon nutrient scarcity downstream of metabolic sensors. NimB5 is then secreted and bind to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.\n\nAuthor summaryDrosophila larval hemocytes (blood cells) are found in two compartments: the lymph gland considered as a reservoir, and the peripheral compartment. Peripheral hemocytes form sessile patches attached to the internal surface of the larval body wall or are found freely circulating in the hemolymph. Little is known about the signals that regulate hemocytes proliferation and localization in the peripheral compartment. In this study, we have identified a new gene, NimrodB5, coding for the NimB5 protein, which is secreted by the fat body and binds to hemocytes. NimB5 inhibits hemocyte proliferation while promoting sessility, leading to an increased number of circulating hemocytes and adhesion defects in NimB5 mutant. We show that nimrodB5 expression by the fat body is controlled by metabolic cues to adjust hemocyte number to the physiological state of the larvae.\n\nInterestingly, deregulation of NimB5 causes lethality when larvae are raised on a poor diet due to a defect in regulating hemocytes proliferation. In conclusion, we have identified a new adipokine that optimizes hemocytes number to the physiological state of larvae. Our study also reveals a major role of the fat body in peripheral hematopoiesis regulation and outline how it can be costly to maintain a basal immune defense.

immunology↗