Intracellular C3 protects β-cells from IL-1β-driven cytotoxicity via interaction with Fyn-related kinase.

One of the hallmarks of type 1 but also type 2 diabetes is pancreatic islet inflammation, associated with altered pancreatic islet function and structure, if unresolved. IL-1β is a proinflammatory cytokine which detrimentally affects β-cell function. In the course of diabetes, complement components, including the central complement protein C3, are deregulated.

Alternative translation and retrotranslocation of cytosolic C3 that detects cytoinvasive bacteria.

Complement C3 was originally regarded as a serum effector protein, although recent data has emerged suggesting that intracellular C3 can also regulate basic cellular processes. Despite the growing interest in intracellular C3 functions, the mechanism behind its generation has not been demonstrated. In this study we show that C3 can be expressed from an alternative translational start site, resulting in C3 lacking the signal peptide, which is therefore translated in the cytosol.

Interaction of with extracellular matrix components resulting in immunomodulation and bacterial eradication.

is a major human pathogen that causes a variety of diseases ranging from mild skin and throat infections to fatal septicemia. In severe invasive infections, encounters and interacts with components of the extracellular matrix (ECM), including small leucine rich-proteoglycans (SLRPs). In this study, we report a novel antimicrobial role played by SLRPs biglycan, decorin, fibromodulin and osteoadherin, specifically in promoting the eradication of in a human sepsis model of infection.

Antibacterial Fusion Proteins Enhance Killing.

is a human-specific commensal of the respiratory tract and an opportunistic pathogen. It is one of the leading cause of otitis media in children and of acute exacerbations in patients with chronic obstructive pulmonary disease, resulting in significant morbidity and economic burden. Vaccines and new immunotherapeutic strategies to treat this emerging pathogen are needed.

Outside in: Roles of complement in autophagy.

The complement system is a well-characterized cascade of extracellular serum proteins that is activated by pathogens and unwanted waste material. Products of activated complement signal to the host cells via cell surface receptors, eliciting responses such as removal of the stimulus by phagocytosis. The complement system therefore functions as a warning system, resulting in removal of unwanted material.

c-Myc is a novel virulence factor by proxy that targets the host miRNA system and is essential for survival in human macrophages.

species are intracellular protozoan pathogens that have evolved to successfully infect and deactivate host macrophages. How this deactivation is brought about is not completely understood. Recently, microRNAs (miRNAs) have emerged as ubiquitous regulators of macrophage gene expression that contribute to shaping the immune responses to intracellular pathogens.

Leishmania donovani chaperonin 10 regulates parasite internalization and intracellular survival in human macrophages.

Protozoa of the genus Leishmania infect macrophages in their mammalian hosts causing a spectrum of diseases known as the leishmaniases. The search for leishmania effectors that support macrophage infection is a focus of significant interest. One such candidate is leishmania chaperonin 10 (CPN10) which is secreted in exosomes and may have immunosuppressive properties.

Phenotypic Characterization of a Leishmania donovani Cyclophilin 40 Null Mutant.

Protozoan parasites of the genus Leishmania adapt to their arthropod and vertebrate hosts through the development of defined life cycle stages. Stage differentiation is triggered by environmental stress factors and has been linked to parasite chaperone activities. Using a null mutant approach we previously revealed important, nonredundant functions of the cochaperone cyclophilin 40 in L.

HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh) Subsets and Skewed B Cell Maturation.

Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+) individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined.