Septins in Infections: Focus on Viruses.

Human septins comprise a family of 13 genes that encode conserved GTP-binding proteins. They form nonpolar complexes, which assemble into higher-order structures, such as bundles, scaffolding structures, or rings. Septins are counted among the cytoskeletal elements. They interact with the actin and microtubule networks and can bind to membranes. Many cellular functions with septin participation have been described in the literature, including cytokinesis, motility, forming of scaffolding platforms or lateral diffusion barriers, vesicle transport, exocytosis, and recognition of micron-scale curvature. Septin dysfunction has been implicated in diverse human pathologies, including neurodegeneration and tumorigenesis. Moreover, septins are thought to affect the outcome of host-microbe interactions. Implication of septins has been demonstrated in fungal, bacterial, and viral infections. Knowledge on the precise function of a particular septin in the different steps of the virus infection and replication cycle is still limited. Published data for vaccinia virus (VACV), hepatitis C virus (HCV), influenza A virus (H1N1 and H5N1), human herpesvirus 8 (HHV-8), and Zika virus (ZIKV), all of major concern for public health, will be discussed here.

Chemotaxis and swarming in differentiated HL-60 neutrophil-like cells.

The human leukemia cell line (HL-60) is an alternative to primary neutrophils in research studies. However, because HL-60 cells proliferate in an incompletely differentiated state, they must undergo differentiation before they acquire the functional properties of neutrophils. Here we provide evidence of swarming and chemotaxis in differentiated HL-60 neutrophil-like cells (dHL-60) using precise microfluidic assays. We found that dimethyl sulfoxide differentiated HL-60 cells (DdHL-60) have a larger size, increased length, and lower ability to squeeze through narrow channels compared to primary neutrophils. They migrate through tapered microfluidic channels slower than primary neutrophils, but faster than HL-60s differentiated by other protocols, e.g., using all-trans retinoic acid. We found that dHL-60 can swarm toward zymosan particle clusters, though they display disorganized migratory patterns and produce swarms of smaller size compared to primary neutrophils.

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system.

Microglia cells are the unique residential macrophages of the central nervous system (CNS). They have a special origin, as they derive from the embryonic yolk sac and enter the developing CNS at a very early stage. They play an important role during CNS development and adult homeostasis. They have a major contribution to adult neurogenesis and neuroinflammation. Thus, they participate in the pathogenesis of neurodegenerative diseases and contribute to aging. They play an important role in sustaining and breaking the blood-brain barrier. As innate immune cells, they contribute substantially to the immune response against infectious agents affecting the CNS. They play also a major role in the growth of tumours of the CNS. Microglia are consequently the key cell population linking the nervous and the immune system. This review covers all different aspects of microglia biology and pathology in a comprehensive way.

Regulation of porcine plasmacytoid dendritic cells by cytokines.

Plasmacytoid dendritic cells (pDC) are the most potent producers of type-I interferon (IFN) and represent the main interferon (IFN)-α source in response to many viruses. Considering the important roles played by type I IFN's, not only as antiviral effectors but also as potent alarming cytokine of the immune system, we investigated how such responses are regulated by various cytokines. To this end, we stimulated enriched pDC in the presence or absence of particular cytokines with a strong activator, CpG DNA, or a weak activator of pDC, foot-and-mouth disease virus (FMDV). Alternatively, we pre-incubated pDC for 16 h before stimulation. The pro-inflammatory cytokines tested Interleukin (IL)-6, IL17A, tumour necrosis factor (TNF)-α did not influence IFN-α responses except TNF-α, which promoted responses induced by FMDV. The haematopoietic cytokines Fms-related tyrosine kinase 3 ligand (Flt3-L) and granulocyte-macrophage colony-stimulating factor (GM-CSF) had enhancing effects on pDC activation at least in one of the protocols tested. IFN-ß and IFN-γ were the most potent at enhancing FMDV-induced IFN-α, up to 10-fold. Interestingly, also the Th2 cytokine IL-4 was an efficient promoter of pDC activity, while IL-10 was the only negative regulator of IFN-α in pDC identified. The cytokines enhancing IFN-α responses also promoted pDC survival in cell culture with the exception of GM-CSF. Taken together this work illustrates how the cytokine network can influence pDC activation, a knowledge of relevance for improving vaccines and therapeutic interventions during virus infections, cancers and autoimmune diseases in which pDC play a role.