Fibulins and cancer: friend or foe?

The fibulins are a family of secreted glycoproteins, which are characterised by repeated epidermal-growth-factor-like domains and a unique C-terminal structure. Six distinct fibulin genes, encoding at least nine protein products generated by alternative splicing, have been identified. Considerable evidence is available pointing towards a structural role for fibulins within the extracellular matrix. Fibulins have been shown to modulate cell morphology, growth, adhesion and motility. The dysregulation of certain fibulins occurs in a range of human disorders, including cancer. Indeed, both tumour suppressive and oncogenic activities have been proposed for members of the fibulin family. Herein, we discuss the possible roles of fibulins in cancer, in addition to their diagnostic and therapeutic potential.     

Cardiac fibroblasts: friend or foe?

Cardiac function is determined by the dynamic interaction of various cell types and the extracellular matrix that composes the heart. This interaction varies with the stage of development and the degree and duration of mechanical, chemical, and electrical signals between the various cell types and the ECM. Understanding how these complex signals interact at the molecular, cellular, and organ levels is critical to understanding the function of the heart under a variety of physiological and pathophysiological conditions. Quantitative approaches, both in vivo and in vitro, are essential to understand the dynamic interaction of mechanical, chemical, and electrical stimuli that govern cardiac function. The fibroblast can thus be a friend in normal function or a foe in pathophysiological conditions.     

Chlamydiales and the innate immune response: friend or foe?

Pathogenicity of Chlamydia and Chlamydia-related bacteria could be partially mediated by an enhanced activation of the innate immune response. The study of this host pathogen interaction has proved challenging due to the restricted in vitro growth of these strict intracellular bacteria and the lack of genetic tools to manipulate their genomes. Despite these difficulties, the interactions of Chlamydiales with the innate immune cells and their effectors have been studied thoroughly. This review aims to point out the role of pattern recognition receptors and signal molecules (cytokines, reactive oxygen species) of the innate immune response in the pathogenesis of chlamydial infection. Besides inducing clearance of the bacteria, some of these effectors may be used by the Chlamydia to establish chronic infections or to spread. Thus, the induced innate immune response seems to be variable depending on the species and/or the serovar, making the pattern more complex. It remains crucial to determine the common players of the innate immune response in order to help define new treatment strategies and to develop effective vaccines. The excellent growth in phagocytic cells of some Chlamydia-related organisms such as Waddlia chondrophila supports their use as model organisms to study conserved features important for interactions between the innate immunity and Chlamydia.     

Inflammation in viral myocarditis: friend or foe?

Viral myocarditis is an important cause of heart failure for which no specific treatments are available. Direct viral injury to cardiac cells provokes an inflammatory response that significantly contributes to cardiac damage and ensuing morbidity. Despite the central pathogenic role of autoimmune injury, broad inhibition of the inflammatory response does not result in patient benefit. Many preclinical studies collectively emphasize that modulating distinct inflammatory signaling pathways may yield effective viral clearance while preserving cardiac structure. This review aims to provide an overview of the sometimes contrasting observations from experimental viral myocarditis models and to translate the lessons learned into opportunities for future investigations and therapies.     

Parasites in biodiversity conservation: friend or foe?

Parasites stabilise food webs and facilitate species coexistence but can also lead to population- or species-level extinctions. So, in biodiversity conservation, are parasites friends or foes? This question is misleading: it implies that parasites are not part of biodiversity. Greater integration of parasites into global biodiversity and ecosystem conservation efforts is required.     

Amyloid in neurodegenerative diseases: friend or foe?

Accumulation of amyloid-like aggregates is a hallmark of numerous neurodegenerative disorders such as Alzheimer's and polyglutamine disease. Yet, whether the amyloid inclusions found in these diseases are toxic or cytoprotective remains unclear. Various studies suggest that the toxic culprit in the amyloid folding pathway is actually a soluble oligomeric species which might interfere with normal cellular function by a multifactorial mechanism including aberrant protein-protein interactions. Molecular chaperones suppress toxicity of amyloidogenic proteins by inhibiting aggregation of non-native disease substrates and targeting them for refolding or degradation. Paradoxically, recent studies also suggest a protective action of chaperones in their promotion of the assembly of large, tightly packed, benign aggregates that sequester toxic protein species.