Macrophage variants in laboratory research: most are well done, but some are RAW.

Macrophages play a pivotal role in the innate immune response. While their most characteristic function is phagocytosis, it is important not to solely characterize macrophages by this activity. Their crucial roles in body development, homeostasis, repair, and immune responses against pathogens necessitate a broader understanding.

Simultaneous Increases in Intracellular Sodium and Tonicity Boost Antimicrobial Activity of Macrophages.

Inflamed and infected tissues can display increased local sodium (Na) levels, which can have various effects on immune cells. In macrophages, high salt (HS) leads to a Na/Ca-exchanger 1 (NCX1)-dependent increase in intracellular Na levels. This results in augmented osmoprotective signaling and enhanced proinflammatory activation, such as enhanced expression of type 2 nitric oxide synthase and antimicrobial function.

The influence of negative pressure wound therapy on bacterial and fungal growth.

Background: The use of negative pressure wound therapy (NPWT) in superinfected wounds is controversial. The mechanism of action is unclear, but recent studies have shown lower atmospheric oxygen levels within the dressing. Therefore, different oxygen-favoring bacteria and fungi might benefit or face impaired thriving conditions.

Macrophages inhibit Coxiella burnetii by the ACOD1-itaconate pathway for containment of Q fever.

Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis-aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever.

Acidic Microenvironments Found in Cutaneous Lesions Curtail NO-Dependent Antiparasitic Macrophage Activity.

Local tissue acidosis affects anti-tumor immunity. In contrast, data on tissue pH levels in infected tissues and their impact on antimicrobial activity is sparse. In this study, we assessed the pH levels in cutaneous lesions.

Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis.

Sensing of pathogens by pattern recognition receptors (PRR) is critical to initiate protective host defence reactions. However, activation of the immune system has to be carefully titrated to avoid tissue damage necessitating mechanisms to control and terminate PRR signalling. Dectin-1 is a PRR for fungal β-glucans on immune cells that is rapidly internalised after ligand-binding.

MODISSA: a multipurpose platform for the prototypical realization of vehicle-related applications using optical sensors.

We present the current state of development of the sensor-equipped car MODISSA, with which Fraunhofer IOSB realizes a configurable experimental platform for hardware evaluation and software development in the context of mobile mapping and vehicle-related safety and protection. MODISSA is based on a van that has successively been equipped with a variety of optical sensors over the past few years, and contains hardware for complete raw data acquisition, georeferencing, real-time data analysis, and immediate visualization on in-car displays. We demonstrate the capabilities of MODISSA by giving a deeper insight into experiments with its specific configuration in the scope of three different applications.

High Na Environments Impair Phagocyte Oxidase-Dependent Antibacterial Activity of Neutrophils.

Infection and inflammation can augment local Na abundance. These increases in local Na levels boost proinflammatory and antimicrobial macrophage activity and can favor polarization of T cells towards a proinflammatory Th17 phenotype. Although neutrophils play an important role in fighting intruding invaders, the impact of increased Na on the antimicrobial activity of neutrophils remains elusive.

Effects of mechanical strain on periodontal ligament fibroblasts in presence of Aggregatibacter actinomycetemcomitans lysate.

Purpose: Many adult orthodontic patients suffer from periodontitis, which is caused by oral pathogens such as the gram-negative Aggregatibacter actinomycetemcomitans (Agac). Like orthodontic tooth movement, periodontitis is associated with inflammation and alveolar bone remodelling thereby affecting orthodontic treatment. Interactions of both processes, however, are not sufficiently explored, particularly with regard to oxidative stress.

Differential gene expression response of synovial fibroblasts from temporomandibular joints and knee joints to dynamic tensile stress.

Purpose: Apart from other risk factors, mechanical stress on joints can promote the development of osteoarthritis (OA), which can also affect the temporomandibular joint (TMJ), resulting in cartilage degeneration and synovitis. Synovial fibroblasts (SF) play an important role in upkeeping joint homeostasis and OA pathogenesis, but mechanical stress as a risk factor might act differently depending on the type of joint. We thus investigated the relative impact of mechanical stress on the gene expression pattern of SF from TMJs and knee joints to provide new insights into OA pathogenesis.

Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint.

Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h.

Mechanisms controlling bacterial infection in myeloid cells under hypoxic conditions.

Various factors of the tissue microenvironment such as the oxygen concentration influence the host-pathogen interaction. During the past decade, hypoxia-driven signaling via hypoxia-inducible factors (HIF) has emerged as an important factor that affects both the pathogen and the host. In this chapter, we will review the current knowledge of this complex interplay, with a particular emphasis given to the impact of hypoxia and HIF on the inflammatory and antimicrobial activity of myeloid cells, the bacterial responses to hypoxia and the containment of bacterial infections under oxygen-limited conditions.

Self-Calibration for the Time Difference of Arrival Positioning.

The time-difference-of-arrival (TDOA) self-calibration is an important topic for many applications, such as indoor navigation. One of the most common methods is to perform nonlinear optimization. Unfortunately, optimization often gets stuck in a local minimum.

Decawave UWB Clock Drift Correction and Power Self-Calibration.

The position accuracy based on Decawave Ultra-Wideband (UWB) is affected mainly by three factors: hardware delays, clock drift, and signal power. This article discusses the last two factors. The general approach to clock drift correction uses the phase-locked loop (PLL) integrator, which we show is subject to signal power variations, and therefore, is less suitable for clock drift correction.

Mononuclear phagocytes orchestrate prolyl hydroxylase inhibition-mediated renoprotection in chronic tubulointerstitial nephritis.

Prolyl hydroxylase domain enzyme inhibitors (PHDIs) stabilize hypoxia-inducible factors (HIFs), and are protective in models of acute ischemic and inflammatory kidney disease. Whether PHDIs also confer protection in chronic inflammatory kidney disease models remains unknown. Here we investigated long-term effects of PHDI treatment in adenine-induced nephropathy as a model for chronic tubulointerstitial nephritis.

HIF1A and NFAT5 coordinate Na-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting.

Infection and inflammation are able to induce diet-independent Na-accumulation without commensurate water retention in afflicted tissues, which favors the pro-inflammatory activation of mouse macrophages and augments their antibacterial and antiparasitic activity. While Na-boosted host defense against the protozoan parasite is mediated by increased expression of the leishmanicidal NOS2 (nitric oxide synthase 2, inducible), the molecular mechanisms underpinning this enhanced antibacterial defense of mouse macrophages with high Na (HS) exposure are unknown. Here, we provide evidence that HS-increased antibacterial activity against was neither dependent on NOS2 nor on the phagocyte oxidase.

Limitation of TCA Cycle Intermediates Represents an Oxygen-Independent Nutritional Antibacterial Effector Mechanism of Macrophages.

In hypoxic and inflamed tissues, oxygen (O)-dependent antimicrobial defenses are impaired due to a shortage of O. To gain insight into the mechanisms that control bacterial infection under hypoxic conditions, we infected macrophages with the obligate intracellular pathogen Coxiella burnetii, the causative agent of Q fever. Our experiments revealed that hypoxia impeded C.

Dectin-1 Positive Dendritic Cells Expand after Infection with Parasites and Represent Promising Targets for Vaccine Development.

Resistant mouse strains mount a protective T cell-mediated immune response upon infection with (L.) parasites. Healing correlates with a T helper (Th) cell-type 1 response characterized by a pronounced IFN-γ production, while susceptibility is associated with an IL-4-dependent Th2-type response.

Hypoxia, Hypoxia-Inducible Factor-1α, and Innate Antileishmanial Immune Responses.

Low oxygen environments and accumulation of hypoxia-inducible factors (HIFs) are features of infected and inflamed tissues. Here, we summarize our current knowledge on oxygen levels found in -infected tissues and discuss which mechanisms potentially contribute to local tissue oxygenation in leishmanial lesions. Moreover, we review the role of hypoxia and HIF-1 on innate antileishmanial immune responses.

Salt-responsive gut commensal modulates T17 axis and disease.

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (T17) cells, which can also contribute to hypertension. Induction of T17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown.

Myeloid Cell-Derived HIF-1α Promotes Control of Leishmania major.

Hypoxia-inducible factor-1α (HIF-1α), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. However, whether and to what extent HIF-1α expressed by myeloid cells contributes to the innate immune response against Leishmania major parasites is unknown. We observed that Leishmania-infected humans and L.

Elementary immunology: Na as a regulator of immunity.

The skin can serve as an interstitial Na reservoir. Local tissue Na accumulation increases with age, inflammation and infection. This increased local Na availability favors pro-inflammatory immune cell function and dampens their anti-inflammatory capacity.

Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen.

Both hypoxic and inflammatory conditions activate transcription factors such as hypoxia-inducible factor (HIF)-1α and nuclear factor (NF)-κB, which play a crucial role in adaptive responses to these challenges. In dendritic cells (DC), lipopolysaccharide (LPS)-induced HIF1α accumulation requires NF-κB signaling and promotes inflammatory DC function. The mechanisms that drive LPS-induced HIF1α accumulation under normoxia are unclear.

High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt.