Metabolic Recovery with the Persistence of Proinflammatory Leucocyte Dysfunction After Bariatric Intervention for Obesity.

PURPOSE: A suitable option for severe obesity treatment is a surgical approach. After surgery, metabolic markers and weight frequently return to adequate values; however, concerning systemic inflammatory mediators, the results are inconsistent. Furthermore, it has been suggested that leucocyte function may be affected even after weight normalization. This study aimed to determine if the surgical treatment of obesity influences the production of cytokines by LPS-stimulated as a function of leucocytes. MATERIALS AND METHODS: We performed a cross-sectional study that investigated the production of cytokines in response to lipopolysaccharide (LPS) along a kinetic of simulation by leucocytes recovered from individuals with normal weight (NW, n = 8), persons living with obesity (Ob, n = 7), persons living with obesity and diabetes mellitus (Ob-DM, n = 17), and persons that used to live with obesity who underwent bypass surgery (fOb + bypass, n = 8) and recover normal weigh. RESULTS: IL-6 levels were significantly higher in the Ob and fOb + bypass groups than in NW (p = 0.043). IL-10 secretion without LPS was significantly higher in the NW group than in the other groups explored (p < 0.05). When exposed to LPS, the IL-10 levels increased in all groups except the NW group. As also observed for IL-18 and IL-33, the secretion curve of the fOb + bypass group was more similar to the Ob group, even when they had reached normal weight, as opposed to the NW group. CONCLUSION: Our results show that in patients with fOb + bypass, inflammatory and anti-inflammatory cytokine production dynamics remain disrupted even with improved metabolic control and normal weight recovery.

LprG and PE_PGRS33 Mycobacterium tuberculosis virulence factors induce differential mitochondrial dynamics in macrophages.

The interaction of a pathogen with its host cell takes place at different levels, including the bioenergetics adaptation of both the pathogen and the host cell in the course of an infection. In this regard, Mycobacterium tuberculosis infection of macrophages induces mitochondrial membrane potential (Δψm) changes and cytochrome c release, depending on the bacteria strain's virulence, and the mitochondrial dynamics is modified by pathogens, such as Listeria monocytogenes. Here, we investigated whether two M. tuberculosis virulence factors are able to induce distinguishable bioenergetics traits in human monocyte-derived macrophages (MDMs). Results showed that Rv1411c (LprG, p27) induced mitochondrial fission, lowered the cell respiratory rate and modified the kinetics of mitochondrial Ca2+ uptake in response to agonist stimulation. In contrast, Rv1818c (PE_PGRS33) induced mitochondrial fusion, but failed to induce any appreciable effect on cell respiratory rate or mitochondrial Ca2+ uptake. Overall, these results suggest that two different virulence factors from the same pathogen (M. tuberculosis) induce differential effects on mitochondrial dynamics, cell respiration and mitochondrial Ca2+ uptake in MDMs. The timing of differential mitochondrial activity could ultimately determine the outcome of host-pathogen interactions.

Dengue Virus Serotype-2 Interferes with the Formation of Neutrophil Extracellular Traps.

OBJECTIVES: Neutrophils play an important role in the control of pathogens through several mechanisms, including phagocytosis and the formation of neutrophil extracellular traps (NETs). The latter consists of DNA as a backbone with embedded antimicrobial peptides, histones, and proteases, providing a matrix to entrap and in some cases to kill microbes. Some metabolic requirements for NET formation have recently been described. The virus-induced formation of NETs and the role of these traps in viral infections remain scarcely reported. Here, we analyzed whether dengue virus serotype-2 (DENV-2) induces NET formation and the DENV-2 effect on phorbol myristate acetate (PMA)-induced NETs. METHODS: Peripheral blood-derived neutrophils were exposed in vitro to DENV-2 or exposed to DENV-2 and then stimulated with PMA. NET formation was assessed by fluorescence microscopy. Cell membrane Glut-1, glucose uptake, and reactive oxygen species (ROS) production were assessed. RESULTS: DENV-2 does not induce the formation of NETs. Moreover, DENV-2 inhibits PMA-induced formation of NETs by about 80%. This effect is not related to the production of ROS. The mechanism seemingly accountable for this inhibitory effect is the DENV-2-mediated inhibition of PMA-induced glucose uptake by neutrophils. CONCLUSION: Our results suggest that DENV-2 inhibits glucose uptake as a metabolism-based way to avoid the formation of NETs.