Anette Christ

University of Bonn | Uni Bonn · Institute of Innate Immunity

Chronic low-grade inflammation, also called metaflammation, is associated with prevalent non-communicable diseases, such as atherosclerosis. Anti-inflammatory therapy provides a clinical benefit in patients, but the triggers that incite metaflammation remain largely unknown. To uncover non-genetic inflammatory factors influencing atherosclerosis se...

Background: Pathogens or trauma-derived danger signals induced maturation and activation of plasmacytoid dendritic cells (pDCs) is a pivotal step in pDC-dependent host defense. Exposure of pDC to cardiometabolic disease-associated lipids and proteins may well influence critical signaling pathways, thereby compromising immune responses against endo...

Chronic HIV infection may exacerbate atherosclerotic vascular disease, which at advanced stages presents as necrotic plaques rich in crystalline cholesterol. Such lesions can catastrophically rupture precipitating myocardial infarct and stroke, now important causes of mortality in those living with HIV. However, in this population little is known a...

Changes in modern dietary habits such as consumption of Western-type diets affect physiology on several levels, including metabolism and inflammation. It is currently unclear whether changes in systemic metabolism due to dietary interventions are long-lasting and affect acute inflammatory processes. Here, we investigated how high-fat diet (HFD) fee...

Toll-like receptor (TLR) activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades. Whether concurrent changes in the cellular metabolism that occur upon TLR activation influence the quality of the transcriptional responses remains unknown. Here, we investigated how macrophages adopt their me...

The consumption of Western-type calorically rich diets combined with chronic overnutrition and a sedentary lifestyle in Western societies evokes a state of chronic metabolic inflammation, termed metaflammation. Metaflammation contributes to the development of many prevalent non-communicable diseases (NCDs), and these lifestyle-associated pathologie...

Objective: Patients with hypomorphic mutations in DNase II develop a severe and debilitating autoinflammatory disease. The objectives of this study were to compare disease parameters of these patients to a murine model of DNase II deficiency, evaluate the role of specific nucleic acid sensors and identify cell types responsible for driving the aut...

Chronic consumption of a Western diet along with sedentary behaviour causes chronic metabolic inflammation (termed metaflammation) and is ‘memorized’ by innate immune cells through long-lasting metabolic and epigenetic cellular reprogramming. Lifestyle-associated pathologies have reached epidemic proportions and require a better understanding of th...

Background TLR9 appears to play both a protective and a disease-promoting role in animal models of SLE. Even though TLR9 is required for the production of anti-dsDNA and anti-nucleosome autoantibodies, TLR9-deficient autoimmune-prone mice invariably develop more severe disease than their TLR9-sufficient counterparts. Molecular mechanisms that accou...

Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling c...

Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity," causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (W...

Systemic lupus erythematosus (SLE) is a chronic, life-threatening autoimmune disorder, leading to multiple organ pathologies and kidney destruction. Analyses of numerous murine models of spontaneous SLE have revealed a critical role for endosomal TLRs in the production of autoantibodies and development of other clinical disease manifestations. Neve...

Efforts to reverse the pathologic consequences of vulnerable plaques are often stymied by the complex treatment resistant pro-inflammatory environment within the plaque. This suggests that pro-atherogenic stimuli, such as LDL cholesterol and high fat diets may impart longer lived signals on (innate) immune cells that persist even after reversing th...

Summary Host-microbiome co-evolution drives homeostasis and disease susceptibility, yet regulatory principles governing the integrated intestinal host-commensal microenvironment remain obscure. While inflammasome signaling participates in these interactions, its activators and microbiome-modulating mechanisms are unknown. Here, we demonstrate that...

The contribution of both innate and adaptive immune processes to the pathophysiology of atherosclerosis is undisputed. Next to cytokines, a range of danger-associated molecular pattern molecules (DAMP) are being released in plaque, amongst others by apoptotic and necrotic cells and due to proteolysis of extracellular matrix material. These proinfla...

This editorial refers to 'LOX-1, mtDNA damage, and NLRP3 inflammasome activation in macrophages: implications in atherogenesis' by Z. Ding et al., pp. 619-628, this issue.

Objective: Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing disorder that may develop in patients with chronic kidney disease after administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis subsequently develops. However, the preci...

Cardiovascular diseases (CVDs) are one of the leading causes of mortality worldwide.1 It has been so for decades, notwithstanding a wide array of – mostly preventive – treatment modalities targeting known risk factors, such as hyperlipidemia, type 2 diabetes mellitus, hypertension, or obesity. Recent technical and conceptual advances have unveiled...

Purpose: Plasmacytoid dendritic cells (pDCs) play a pivotal role in orchestrating immunity and tolerance, and as such, they are key targets for immunotherapy. It has been shown that pDCs populate the inflamed human atherosclerotic plaque, thus proposing a pro-inflammatory role through release of type I interferons (IFNs). However, a functional role...

The self-renewal and differentiation capacity of hematopoietic stem and progenitor cells (HSPCs) is an important regulator of the way the mature immune system behaves and how it reacts upon challenges. The co-stimulatory protein CD40L is well-known for its role in immune activation and chronic inflammatory diseases, especially in atherosclerosis. W...

Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type I interferon response. Though proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive. To investigate the role of PDC in atherosclerosis. We show that PDC are scarcely present in human ath...

Obese adipose tissue shows hallmarks of chronic inflammation, which promotes the development of metabolic disorders. The mechanisms by which immune cells interact with each other or with metabolism-associated cell types, and the players involved, are still unclear. The CD40-CD40L costimulatory dyad plays a pivotal role in immune responses and in di...

Plasmacytoid dendritic cells (pDC) have been shown to play a pivotal immunogenic role in viral immune responses by releasing high IFN-alpha levels upon TLR9 activation. However, evidence is culminating that pDC also play a major role in inducing immune tolerance in chronic low grade inflammation. In this study we set out to address effects of pDC d...