No abstract

Infection with flaviviruses causes mild to severe diseases, including viral hemorrhagic fever, vascular shock syndrome, and viral encephalitis. Several animal models explore the pathogenesis of viral encephalitis, as shown by neuron destruction due to neurotoxicity after viral infection. While neuronal cells are injuries caused by inflammatory cytokine production following microglial/macrophage activation, the blockade of inflammatory cytokines can reduce neurotoxicity to improve the survival rate. This study investigated the involvement of macrophage phenotypes in facilitating CNS inflammation and neurotoxicity during flavivirus infection, including the Japanese encephalitis virus, dengue virus (DENV), and Zika virus. Mice infected with different flaviviruses presented encephalitis-like symptoms, including limbic seizure and paralysis. Histology indicated that brain lesions were identified in the hippocampus and surrounded by mononuclear cells. In those regions, both the infiltrated macrophages and resident microglia were significantly increased. RNA-seq analysis showed the gene profile shifting toward type 1 macrophage (M1) polarization, while M1 markers validated this phenomenon. Pharmacologically blocking C-C chemokine receptor 2 and tumor necrosis factor-α partly retarded DENV-induced M1 polarization. In summary, flavivirus infection, such as JEV and DENV, promoted type 1 macrophage polarization in the brain associated with encephalitic severity.

Background: Phorbol 12-myristate 13-acetate (PMA)-induced differentiation of human monocytic THP-1 cells is an experimental model for preparing resting macrophages (M 0 ) for cell polarization toward the different functional specializations of macrophages. Methods: In this study, we examined the expression of immune checkpoints by using flow cytometry following multicolor staining. The blockade of immune checkpoint by using neutralizing antibodies was performed to assess their role in PMA-induced THP-1-differentiated macrophages. Results: Upon the inducible macrophage differentiation caused by PMA, increased expression levels of CD11b and CD68 were measured and characterized according to their adherent phenotype accompanied by the generation of cellular complexity. While the cell growth rate was abolished post-differentiation, some cells underwent cell death. Notably, we found increases in the expression of programmed cell death protein 1, also known as PD-1 (CD279), and its ligand PD-L1 (CD274), mainly in differentiated M 0 (CD68 + CD11b + ) macrophages. However, neutralizing PD-L1/PD-1 neither blocked THP-1 cell differentiation toward macrophages nor inhibited macrophage polarization in M 1 and M 2 . In specializing macrophages, a decrease both in CD274 and CD279 was found in M 2 . Conclusion: These results revealed the inducible expression of PD-L1/PD-1 in PMAinduced THP-1-differentiated M 0 macrophages followed by a decrease in M 2 macrophages.

Dengue fever is an infection by the dengue virus (DENV) transmitted by vector mosquitoes. It causes many infections in tropical and subtropical countries every year, thus posing a severe disease threat. Cytokine storms, one condition where many proinflammatory cytokines are mass-produced, might lead to cellular dysfunction in tissue/organ failures and often facilitate severe dengue disease in patients. Interleukin- (IL-) 18, similar to IL-1β, is a proinflammatory cytokine produced during inflammation following inflammasome activation. Inflammatory stimuli, including microbial infections, damage signals, and cytokines, all induce the production of IL-18. High serum IL-18 is remarkably correlated with severely ill dengue patients; however, its possible roles have been less explored. Based on the clinical and basic findings, this review discusses the potential immunopathogenic role of IL-18 when it participates in DENV infection and dengue disease progression based on existing findings and related past studies.

Silver particles were prepared by dewetting Ag films coated on glass using a fiber laser. The size of the particles was controlled in the range of 92 nm–1.2 μm by adjusting the thickness of the Ag film. The structural properties and surface roughness of the particles were evaluated by means of scanning electron microscopy. In addition, the antifungal activity of the Ag particles was examined using spore suspensions of Colletotrichum gloeosporioides. It is shown that particles with a size of 1.2 μm achieved 100% inhibition of conidia growth of C. gloeosporioides after a contact time of just 5 min. Furthermore, the smaller particles also achieved good antifungal activity given a longer contact time. Similar results were observed for spore germination and pathogenicity tests performed on mango fruit and leaves. Overall, the results confirm that Ag particles have an excellent antifungal effect on C. gloeosporioides.