Silver nanoparticles combat Salmonella Typhimurium: Suppressing intracellular infection and activating dendritic cells.

Salmonella Typhimurium (ST) can hide inside cells, avoid antibiotic therapy and being killed by host's immune system to cause persistent infection in humans and animals. Metal nanoparticles are regarded as an alternative to overcome the above limitations, silver nanoparticles especially have been applied in combating drug-resistant bacteria. However, the therapeutic effects of silver nanoparticles against intracellular infection and their impacts on host immunity remain an area of further investigation. In this work, we synthesized Ganoderma extract-capped silver nanoparticles (Ag@Ge) and explored the therapeutic potential and immune adjuvant effects of Ag@Ge against intracellular ST. Firstly, Ag@Ge had a small particle size of 35.52±7.46 nm, good stability, and biocompatibility. Then, Ag@Ge effectively entered RAW 264.7 cells, suppressed intracellular ST infection. Furthermore, Ag@Ge activated mouse dendritic cells (DCs) in vitro, evidenced by increased phenotypic markers (CD80/CD86/CD40/major compatibility complex II (MHCII)) expression and cytokine and chemokine (interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL-2), and chemokine (C-C motif) receptor-7 (CCR-7)) transcription. More notably, the combination of Ag@Ge with inactivated ST recruited intestinal DCs to mitigate ST infection in mice, evidenced by decreased body weight loss and bacterial loads in the tissues (liver, jejunum, and colon), and improved platelets count. The above findings indicate that Ag@Ge has the potential as an alternative nano-antibiotic against intracellular ST infection.

Inhibition of the antigen-presenting ability of dendritic cells by non-structural protein 2 of influenza A virus.

Influenza A viruses (IAV), including human IAV and avian IAV (H9N2 subtype), are recurring of influenza outbreaks worldwide in a wide range of mammalian and avian species. Dendritic cells (DCs) are specialised antigen presenting cells. Although DCs can take up IAV and transmit it to other cells, it still unclear why DCs do not effectively present IAV antigens. In this study, we found that Non-structural protein 2 (NS2) of IAV inhibited the maturation and antigen-presenting ability of DCs. We then examined a potential involvement of microRNAs (miRNAs). Analyses of avian DCs stimulated with avian IAV identified 9 upregulated and 10 downregulated miRNAs. However, nearly none microRNA has been significantly altered by NS2 stimulation. Moreover, we found that NS2 binds to exportin 5 (Xpo5), which inhibited miRNA biogenesis. Thus, hijacking of the miRNA biogenesis pathway appears to be one mechanism by which NS2 impairs antigen presentation. Furthermore, we found that NS2 directly interacts with interferon regulatory factor 3, which also inhibits the antigen-presenting ability of DCs. These results thus indicate that NS2-mediated impairment of antigen presentation by DCs might be a mechanism that contributes to the prevalence of the influenza virus.

From nasal to basal: single-cell sequencing of the bursa of Fabricius highlights the IBDV infection mechanism in chickens.

BACKGROUND: Chickens, important food animals and model organisms, are susceptible to many RNA viruses that invade via the nasal cavity. To determine the nasal entry site of the virus and clarify why avians are susceptible to RNA viruses, infectious bursal disease virus (IBDV) was selected because it is a typical avian RNA virus that infects chickens mainly via the nasal route. RESULTS: First, we found that IBDV infected the posterior part of the nasal cavity in chickens, which is rich in lymphoid tissue and allows the virus to be easily transferred to the blood. Via the blood circulation, IBDV infected peripheral blood mononuclear cells (PBMCs) and was transferred to the bursa of Fabricius to damage the IgM + B lymphocyte population. Subsequently, the single-cell RNA sequencing (scRNA-seq) results suggested the more detailed response of different bursal cell populations (B cells, epithelial cells, dendritic cells, and fibroblasts) to IBDV. Regarding B cells, IBDV infection greatly decreased the IgM + B cell population but increased the IgA + B cell population in the bursal follicles. In contrast to B cells, bursal epithelial cells, especially basal cells, accumulated a large number of IBDV particles. Furthermore, we found that both innate RNA sensors and interferon-stimulated genes (ISGs) were highly expressed in the IBDV-infected groups, while dicer and ago2 expression was largely blocked by IBDV infection. This result suggests that dicer-related RNA interference (RNAi) might be an effective antiviral strategy for IBDV infection in avian. CONCLUSION: Our study not only comprehensively elaborates on the transmission of airborne IBDV via the intranasal route and establishes the main target cell types for productive IBDV infection but also provides sufficient evidence to explain the cellular antiviral mechanism against IBDV infection.

The mechanism of antigen-presentation of avian bone marrowed dendritic cells suppressed by infectious bronchitis virus.

Dendritic cells are first guard to defend avian infectious bronchitis virus (IBV) infection and invasion. While IBV always suppress dendritic cells and escape the degradation and presentation, which might help viruses to transfer and migrant. Initially, we compared two IBV's function in activating avian bone marrow dendritic cells (BMDCs) and found that both IBV (QX and M41) did not significantly increase surface marker of avian BMDCs. Moreover, a significant decrease of m6A modification level in mRNA, but an increased in the ut RNA were observed in avian BMDCs upon the prevalent IBV (QX) infection. Further study found that both non-structural protein 7 (NSP7) and NSP16 inhibited the maturation and cytokines secretion of BMDCs, as well as their antigen-presentation ability. Lastly, we found that gga-miR21, induced by both NSP7 and NSP16, inhibited the antigen presentation of avian BMDCs. Taken together, our results illustrated how IBV inhibited the antigen-presentation of avian DCs.