Crosstalk Between Autophagy and Hypoxia-Inducible Factor-1α in Antifungal Immunity.

Modern medicine is challenged by several potentially severe fungal pathogens such as Aspergillus fumigatus, Candida albicans, or Histoplasma capsulatum. Though not all fungal pathogens have evolved as primary pathogens, opportunistic pathogens can still cause fatal infections in immuno-compromised patients. After infection with these fungi, the ingestion and clearance by innate immune cells is an important part of the host immune response. Innate immune cells utilize two different autophagic pathways, the canonical pathway and the non-canonical pathway, also called microtubule-associated protein 1A/1B-light chain 3 (LC3) -associated pathway (LAP), to clear fungal pathogens from the intracellular environment. The outcome of autophagy-related host immune responses depends on the pathogen and cell type. Therefore, the understanding of underlying molecular mechanisms of autophagy is crucial for the development and improvement of antifungal therapies. One of those molecular mechanisms is the interaction of the transcription-factor hypoxia-inducible factor 1α (HIF-1α) with the autophagic immune response. During this review, we will focus on a comprehensive overview of the role of autophagy and HIF-1α on the outcome of fungal infections.

CD45 in human physiology and clinical medicine.

CD45 is an evolutionary highly conserved receptor protein tyrosine phosphatase exclusively expressed on all nucleated cells of the hematopoietic system. It is characterized by the expression of several isoforms, specific to a certain cell type and the developmental or activation status of the cell. CD45 is one of the key players in the initiation of T cell receptor signaling by controlling the activation of the Src family protein-tyrosine kinases Lck and Fyn. CD45 deficiency results in T- and B-lymphocyte dysfunction in the form of severe combined immune deficiency. It also plays a significant role in autoimmune diseases and cancer as well as in infectious diseases including fungal infections. The knowledge collected on CD45 biology is rather vast, but it remains unclear whether all findings in rodent immune cells also apply to human CD45. This review focuses on human CD45 expression and function and provides an overview on its ligands and role in human pathology.

C1q: A fresh look upon an old molecule.

Originally discovered as part of C1, the initiation component of the classical complement pathway, it is now appreciated that C1q regulates a variety of cellular processes independent of complement activation. C1q is a complex glycoprotein assembled from 18 polypeptide chains, with a C-terminal globular head region that mediates recognition of diverse molecular structures, and an N-terminal collagen-like tail that mediates immune effector mechanisms. C1q mediates a variety of immunoregulatory functions considered important in the prevention of autoimmunity such as the enhancement of phagocytosis, regulation of cytokine production by antigen presenting cells, and subsequent alteration in T-lymphocyte maturation. Furthermore, recent advances indicate additional roles for C1q in diverse physiologic and pathologic processes including pregnancy, tissue repair, and cancer. Finally, C1q is emerging as a critical component of neuronal network refinement and homeostatic regulation within the central nervous system. This review summarizes the classical functions of C1q and reviews novel discoveries within the field.

Cell-Penetrating Bacterial Effector Proteins: Better Tools than Targets.

Bacterial pathogens have developed intriguing virulence mechanisms, including several sophisticated nanomachines, for injecting effector proteins to manipulate host immune signaling pathways for their own benefit. Therefore, bacterial genomes harbor a wealth of information about how to manipulate the defense systems of the host. Current understanding addresses virulence mechanisms mostly as targets for antimicrobials. We propose a change of paradigm by exploiting bacterial effectors not as targets but as tools for the directed manipulation of host signaling - for the benefit of the host. Recently, effector proteins have been identified that autonomously translocate into host cells, representing a novel class of cell-penetrating peptides (CPPs) or effectors (CPEs). Moreover, autonomous cell penetration overcomes a major hurdle in pharmacology by transducing specific therapeutic agents to intracellular targets.

[Cellular in-vitro assays. Applicability in daily routine]. / Zelluläre In-vitro-Allergiediagnostik. Eignung für den klinischen Alltag.

Cellular in-vitro assays are able to detect antigen-dependent cellular processes without any risk for the patient. After antigen stimulation, both the cellular antigen stimulation test assessing sulfidoleukotriene production in leukocyte suspension, and flow cytometric basophil activation assays determining surface activation markers (CD63, CD203c), represent accepted models for in-vivo mast cell stimulation particularly in IgE-dependent reactions of immediate type. The value of these assays should be estimated considering the type of antigen and further diagnostic options. Most studies can not be compared due to different allergen concentrations, conditions of stimulation, methods, and defined cut-offs. Therefore, it is difficult to evaluate published evidence. Because of the logistic effort, cellular assays are often available only in specialized laboratories. However, in daily routine they are important in cases with clear-cut history but negative conventional allergy diagnostic procedures, in case of rare allergens (drugs, exotic food), as well as contraindications for skin and/or provocation test (hymenoptera venom allergy, anaphylaxis).