ABSTRACT Lipid droplets (LDs) are lipid-rich organelles recognized as central players in lipid homeostasis, signaling, and inflammation. While their functions in inflammation are well-documented, the role of LDs in antibacterial immunity and infection resistance remains less understood. In this study, we investigated triglyceride synthesis and LD accumulation in the context of antibacterial innate immunity during sepsis. Our results show that LD accumulation is part of immunometabolic reprogramming in E. coli -infected macrophages. Pharmacological inhibition or genetic knockdown of DGAT1, a key enzyme in triglyceride synthesis, reduced LD formation, bacterial clearance, and pro-inflammatory responses (nitric oxide, PGE 2 , CCL2, IL-6, IFN-β). Notably, DGAT1 inhibition impaired the expression of several interferon-stimulated genes (ISGs), including viperin, iNOS, cathelicidin, and IGTP, in E. coli -infected macrophages. In a sepsis model, DGAT1 inhibition reduced sepsis-induced LD accumulation in peritoneal cells and decreased levels of CCL2, IFN-β, nitric oxide, and lipid mediators (PGE 2 , LTB 4 , and RvD1). Furthermore, DGAT1 inhibition accelerated sepsis-related mortality, coinciding with elevated bacterial loads in the peritoneum and bloodstream at 6 and 24 hours post-sepsis. Our results demonstrate that tryglicerides synthesis and LDs are critical regulators of infection resistance, contributing to both bacterial clearance and the coordination of a protective proinflammatory response during sepsis.

Deep proteomic profiling of rare cell populations has been constrained by sample input requirements. Here, we present DROPPS (droplet-based one-pot preparation for proteomic samples), an accessible low-input platform that generates high-fidelity proteomic profiles of 100-2,500 cells. By applying DROPPS within the mammary epithelium, we elucidated the connection between mitochondrial activity and clonogenicity, identifying CD36 as a marker of progenitor capacity in the basal cell compartment. We anticipate that DROPPS will accelerate biology-driven proteomic research for a multitude of rare cell populations.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed to be the main pathway used by merozoites to invade reticulocytes. However, the increasing number of reports of vivax malaria cases in genotypically Duffy-negative (DN) individuals has raised questions regarding the P. vivax invasion pathway(s). Here, we show that a subset of DN erythroblasts transiently express DARC during terminal erythroid differentiation and that P. vivax merozoites, irrespective of their origin, can invade DARC+ DN erythroblasts. These findings reveal that a large number of DN individuals may represent a silent reservoir of deep P. vivax infections at the sites of active erythropoiesis with low or no parasitemia, and it may represent an underestimated biological problem with potential clinical consequences in sub-Saharan Africa.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

The number of obese people is increasing dramatically worldwide, and one of the major causes of obesity is excess energy due to high-fat diets. Several studies have shown that reducing food and energy intake represents a key intervention or treatment to combat overweight/obesity. Here, we conducted a 12-week energy-restricted dietary intervention for high-fat diet-induced obese mice (C57BL/6J) to investigate the effectiveness of diet change in improving obesity. The results revealed that the diet change from HFD to NFD significantly reduced weight gain and subcutaneous adipose tissue weight in high-fat diet-induced obese mice, providing scientific evidence for the effectiveness of diet change in improving body weight and fat deposition in obese individuals. Regarding the potential explanations for these observations, weight reduction may be attributed to the excessive enlargement of adipocytes in the white adipose tissue of obese mice that were inhibited. Diet change significantly promoted lipolysis in the adipose tissue (eWAT: Adrb3, Plin1, HSL, and CPTA1a; ingWAT: CPT1a) and liver (reduced content of nonesterified fatty acids), and reduced lipogenesis in ingWAT (Dgat2). Moreover, the proportion of proliferative stem cells in vWAT and sWAT changed dramatically with diet change. Overall, our study reveals the phenotypic, structural, and metabolic diversity of multiple tissues (vWAT and sWAT) in response to diet change and identifies a role for adipocyte stem cells in the tissue specificity of diet change.

Deep proteomic profiling of rare cell populations has been constrained by sample input requirements. Here, we present DROPPS, an accessible low-input platform that generates high-fidelity proteomic profiles of 100 - 2,500 cells. By applying DROPPS within the mammary epithelium, we elucidated the connection between mitochondrial activity and clonogenicity, discovering and validating CD36 as a marker of progenitor capacity in the basal cell compartment. We anticipate DROPPS will accelerate biology-driven proteomic research for a multitude of rare cell populations.