Dipalmitoyl-phosphatidylserine-filled cationic maltodextrin nanoparticles exhibit enhanced efficacy for cell entry and intracellular protein delivery in phagocytic THP-1 cells.

Vaccination through the upper respiratory tract is a promising strategy, and particulate antigens, such as antigens associated with nanoparticles, triggered a stronger immune response than the sole antigens. Cationic maltodextrin-based nanoparticles loaded with phosphatidylglycerol (NPPG) are efficient for intranasal vaccination but non-specific to trigger immune cells. Here we focused on phosphatidylserine (PS) receptors, specifically expressed by immune cells including macrophages, to improve nanoparticle targeting through an efferocytosis-like mechanism. Consequently, the lipids associated with NPPG have been substituted by PS to generate cationic maltodextrin-based nanoparticles with dipalmitoyl-phosphatidylserine (NPPS). Both NPPS and NPPG exhibited similar physical characteristics and intracellular distribution in THP-1 macrophages. NPPS cell entry was faster and higher (two times more) than NPPG. Surprisingly, competition of PS receptors with phospho-L-serine did not alter NPPS cell entry and annexin V did not preferentially interact with NPPS. Although the protein association is similar, NPPS delivered more proteins than NPPG in cells. On the contrary, the proportion of mobile nanoparticles (50%), the movement speed of nanoparticles (3 µm/5 min), and protein degradation kinetics in THP-1 were not affected by lipid substitution. Together, the results indicate that NPPS enter cells and deliver protein better than NPPG, suggesting that modification of the lipids of cationic maltodextrin-based nanoparticles may be a useful strategy to enhance nanoparticle efficacy for mucosal vaccination.

Sex-dependent interactions between leptin, wasting and humoral immunity in two ethnic communities of school-aged children differentially exposed to Schistosoma haematobium.

Background: Leptin is a nutritional hormone whose production is generally higher in females. We investigated how leptin is associated with sex dimorphism during urinary schistosomiasis in relation with wasting. Methods: A cross-sectional study was carried out in three villages in northern Senegal. Ninety-eight school-aged children belonging to the Fulani or Wolof villages were enrolled. We performed parasitic diagnosis and anthropometric measurement to evaluate nutritional status. We collected peripheral blood to determine the amount of circulating leptin and immunoglobulin G (IgG), IgG4 and IgE directed to soluble worm antigen preparation (SWAP). Results: The prevalence of Schistosoma haematobium infection was higher among boys regardless of ethnic group, but exposure to parasites did not exacerbate malnutrition. The greater ability of girls to produce leptin was not altered by schistosomiasis and was recovered in both ethnic groups. However, while the usual correlation between leptin and fat storage was preserved in Fulani girls, it was disrupted in Fulani boys, who displayed a remarkable susceptibility for wasting. Finally, we observed that leptin was negatively associated with the level of antibodies in Wolof boys. Conclusions: Leptin can be disconnected from body fat and may exert a sex-dependent influence on host immune response to S. haematobium infection in Senegalese children.