Macrophage Survival Assay Using High Content Microscopy

Macrophages are phagocytic innate immune cells and are the main drivers of inflammation in tissue (Medzhitov, 2008). These cells are associated with cancer together with autoimmune, autoinflammatory, infectious, neurodegenerative and metabolic diseases (Ginhoux and Jung, 2014). In this context, the role of macrophages in inflammation is well-studied, however, the impact of macrophage survival in non-infectious and infectious diseases is largely unknown. Our study showed that the activation of certain pathogen-associated receptors (PRRs) can induce macrophage survival (Eren et al., 2016). We described a molecular mechanism that demonstrated how an obligate intracellular pathogen exploits PRR-induced cell survival (Eren et al., 2016). Thus, further studies are necessary to understand the role of macrophage survival in different disease settings

How to master the host immune system? Leishmania parasites have the solutions!

Infection by protozoan parasites of the genus Leishmania results in the development of leishmaniasis, an increasingly prevalent group of diseases affecting over 12 million people worldwide. Leishmaniasis can have very different outcomes ranging from cutaneous lesions, mucosal lesions to visceralization depending on the species of the infecting parasite and on the immune response developed by the host. As an obligate intracellular parasite, residing within macrophages, Leishmania evolved in strict contact with the host immune system, developing different mechanisms to evade or modulate the immune response. Various types of immune responses are observed during different Leishmania spp. infections, resulting in parasite clearance but also contributing to the pathogenesis, thus increasing the complexity of the course of the disease. Interestingly, depending on the type of leishmaniasis developed, opposite treatment strategies, which either boost or inhibit the inflammatory response, have shown efficacy. In this review, we summarize the contribution of different immune cell types to the development of the anti-leishmanial immune response and the parasite strategies to evade and modulate host immunity. Further, we discuss the involvement of co-infecting pathogens in the determination of the outcome of leishmaniasis and on the effectiveness of treatment and the implication of the immune response for treatment and vaccine development

Behind the Scenes: Nod-Like Receptor X1 Controls Inflammation and Metabolism.

Regulatory Nod-like receptors (NLRs) are a subgroup of the cytosolic NLR family of pathogen recognition receptors (PRRs). These receptors can tune the innate immune responses triggered by the activation of other PRRs by either augmenting or attenuating the activated pro-inflammatory signaling cascades. Nod-like receptor X1 (NLRX1) is the only known mitochondria-associated negative regulatory NLR. NLRX1 attenuates several inflammatory pathways and modulates cellular processes such as autophagy and mitochondrial function following infection or injury. Using both in vitro expression and in vivo experimental models, NLRX1 is extensively described in the context of anti-viral signaling and host-defense against invading pathogens. More recently, NLRX1 has also gained interest in the field of cancer and metabolism where NLRX1 functions to attenuate overzealous inflammation in various inflammatory and autoimmune diseases. However, the exact function of this novel receptor is still under debate and many, often contradictory, mechanisms of action together with cellular localizations have been proposed. Thus, a better understanding of the underlying mechanism is crucial for future research and development of novel therapeutical approaches. Here, we summarize the current findings on NLRX1 and discuss its role in both infectious and inflammatory context

The criminal association of Leishmania parasites and viruses.

In nature, humans infected with protozoan parasites can encounter viruses, which could alter their host immune response. The impact of viruses on human parasitic diseases remains largely unexplored due to the highly sterilized environment in experimental studies and the difficulty to draw a correlation between co-infection and pathology. Recent studies show that viral infections exacerbate pathology and promote dissemination of some Leishmania infections, based on a hyper-inflammatory reaction driven by type I interferons. Thus, not only the infecting parasite species, but also bystander viral infections could be a major determinant of the outcome of Leishmania infection. In this review, we focus on the contribution of viral co-infection to the exacerbation of leishmaniasis's pathology and its possible impact on treatment and vaccination strategies

Guidelines and recommendations on yeast cell death nomenclature

lucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cel- lular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the defi- nition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differ- ential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death rou- tines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the au- thors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the pro- gress of this vibrant field of research

The Dawn of European Animal Rights Law

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Leishmania metacaspase: an arginine-specific peptidase.

The purpose of this chapter is to give insights into metacaspase of Leishmania protozoan parasites as arginine-specific cysteine peptidase. The physiological role of metacaspase in Leishmania is still a matter of debate, whereas its peptidase enzymatic activity has been well characterized. Among the different possible expression systems, metacaspase-deficient yeast cells (Δyca1) have been instrumental in studying the activity of Leishmania major metacaspase (LmjMCA). Here, we describe techniques for purification of LmjMCA and its activity measurement, providing a platform for further identification of LmjMCA substrates