Interferons (IFNs) can serve as the first line of immune defense against viral infection. The identification of IFN-λs 1, 2, 3 & 4 (termed as type III IFNs) has revealed that the antiviral immune response to viruses contains more components than the type I IFNs that have been known for more than 50 years. IFN-λs are IFN-λ1 (IL-29), IFN-λ2 (IL-28a), IFN-λ3 (IL-28b) and IFN-λ4, which resembles IFN-λ3. IFN-λs have type I-IFN-like immune responses and biological activities, but our knowledge of these novel players in the antiviral response is not well established. In this review, we try to describe the current information on the expression and function of IFN-λs in the innate antiviral immune defense and IFN-λ2’s role in regulating and shaping the adaptive immune response. We suggest that IFN-λs are key antiviral cytokines, directly performing an antiviral immune response at epithelial surfaces in the early stages of viral infection, and that these cytokines also skew the balance of Th1 and Th2 cells to Th1 phenotype. In addition, genetic polymorphisms in IFN-λ genes can impair antiviral immune responses in clinical treatment.

Lactic acid bacteria (LAB) are the primary genera of the intestinal flora and have many probiotic functions. In the present study, Lactobacillus rhamnosus GG (LGG) ATCC 53103 was used to treat BALB/c mice. After LGG intervention, both low and high LGG doses were shown to improve the observed OTU, Chao1, ACE, and Shannon indices, while the Simpson index decreased, demonstrating that LGG can promote intestinal microbiota abundance and diversity. Furthermore, LGG treatment increased the abundances of intestinal Firmicutes, Bacteroides and Actinomycetes while reducing that of Proteobacteria. In addition to its effect on gut the microbiota, LGG could also regulate the host immune system. In the present study, we showed that LGG could affect the percentage of CD3⁺ T lymphocytes in the spleens (SPLs), mesenteric lymph nodes (MLNs), Peyer’s patches (PPs) and lamina propria lymphocytes (LPLs) of mice, including total CD3⁺ T, CD3⁺CD4⁺ T, and CD3⁺CD8⁺ T lymphocytes. Furthermore, LGG could effectively increase the expression of Th1-type cytokines (IFN-γ) and Th2 cytokines (IL-4) in CD4⁺ T cells, indicating that the proportion of Th1 and Th2 cells in mice with LGG treatment was in a high equilibrium state compared to the control group. In addition, the IFN-γ/IL-4 ratio was greater than 1 in mice with LGG intervention, suggesting that LGG tends to mediate the Th1 immune response. The results of the present study also showed that LGG upregulated the expression of IL-17 in CD4⁺ T cells and regulated the percentage of CD4⁺CD25⁺Foxp3⁺ Treg cells in various secondary immunological organs, indicating that LGG may promote the balance of Th-17 and Treg cells.

African swine fever virus (ASFV) is a large double-stranded DNA virus that primarily infects porcine macrophages. The ASFV genome encodes a large number of immunosuppressive proteins.

African swine fever virus (ASFV) employs diverse strategies to confront or evade host type I interferon (IFN-I)-induced antiviral responses. Moreover, the mechanisms of this process are largely unknown. Here, we assessed 27 ASFV proteins to determine whether any of them suppressed the cGAS-STING pathway to facilitate immune evasion. Using dual-luciferase assays, we found that ASFV MGF505-7R suppressed the activity of the IFN-β and ISRE promoters and the expression of IFN-I and ISGs. MGF505-7R interacted with IRF7 and TBK1, degrading IRF7 by autophagy, cysteine, and proteasome pathways and TBK1 by the proteasome pathway. Moreover, TBK1 and IRF3 were phosphorylated by cGAS-STING stimulation. Finally, small interfering RNA (siRNA)-based silencing of MGF505-7R enhanced IFN-I antiviral activity. Taken together, these results preliminarily clarified the immune escape mechanism of ASFV MGF505-7R, which provides a potential target for developing antiviral agents.

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationships between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG ( LGG ) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3s) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3s and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor influences various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, to promote their growth and development, suggesting that AhR has a broad impact on intestinal health. In conclusion, our study demonstrated the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock. IMPORTANCE: We observed high expression of the AhR receptor on pig and human ILC3s, although its expression was negligible in mouse ILC3s. ILC3s are closely related to the gut microbiota, particularly the secretion of IL-22 stimulated by microbial signals, which plays a crucial regulatory role in intestinal immunity. In our study, we found that metabolites produced by beneficial gut bacteria interact with ILC3s through AhR, thereby maintaining intestinal immune homeostasis in pigs. Moreover, LGG feeding can enhance the activation of ILC3s and promote IL-22 secretion in the intestines of piglets, ultimately preventing PEDV infection.