Probiotics in livestock feed supplements are considered a replacement for antibiotics that enhance gastrointestinal immunity. Although bacterial cell wall components have been proposed to be associated with probiotic function, little evidence demonstrates that they are responsible for probiotic functions in livestock. The present study demonstrated that lipoteichoic acid (LTA) of Lactobacillus plantarum (Lp.LTA) confers anti-inflammatory responses in porcine intestinal epithelial cell line, IPEC-J2. A synthetic analog of viral double-stranded RNA, poly I:C, dose-dependently induced IL-8 production at the mRNA and protein levels in IPEC-J2 cells. Lp.LTA, but not lipoprotein or peptidoglycan from L. plantarum, exclusively suppressed poly I:C-induced IL-8 production. Compared with LTAs from other probiotic Lactobacillus strains including L. delbrueckii, L. sakei, and L. rhamnosus GG, Lp.LTA had higher potential to suppress poly I:C-induced IL-8 production. Dealanylated or deacylated Lp.LTA did not suppress poly I:C-induced IL-8 production, suggesting that D-alanine and lipid moieties in the Lp.LTA structure were responsible for the inhibition. Furthermore, Lp.LTA attenuated the phosphorylation of ERK and p38 kinase as well as the activation of NF-κB, resulting in decreased IL-8 production. Taken together, these results suggest that Lp.LTA acts as an effector molecule to inhibit viral pathogen-induced inflammatory responses in porcine intestinal epithelial cells.
SARS-CoV-2, the coronavirus strain
that initiated the COVID-19
pandemic, and its subsequent variants present challenges to vaccine
development and treatment. As the coronavirus evades the host innate
immune response at the initial stage of infection, the disease can
have a long nonsymptomatic period. The uridylate-specific endoribonuclease
Nsp15 processes the viral genome for replication and cleaves the polyU
sequence in the viral RNA to interfere with the host immune system.
This study screened natural compounds
in vitro
to
identify inhibitors against Nsp15 from SARS-CoV-2. Three natural compounds,
epigallocatechin gallate (EGCG), baicalin, and quercetin, were identified
as potential inhibitors. Potent antiviral activity of EGCG was confirmed
in plaque reduction neutralization tests with a SARS-CoV-2 strain
(PRNT
50
= 0.20 μM). Because the compound has been
used as a functional food ingredient due to its beneficial health
effects, we theorize that this natural compound may help inhibit viral
replication while minimizing safety issues.
Although the 56-kDa protein of Rickettsia tsutsugamushi has been presumed to play important roles in generating protective immunity against scrub typhus, studies of this protein have been impeded. We used the recombinant 56-kDa protein of R. tsutsugamushi Boryong fused with the maltose-binding protein of Escherichia coli (MBP-Bor56) to analyze its ability to induce protective immunity in a C3H/HeDub murine model. Intraperitoneal immunization of mice with MBP-Bor56 resulted in an increase in the 50% minimal lethal dose of more than 160 times compared with that for the control mice. Splenic mononuclear cells from the mice immunized with MBP-Bor56 showed a dose-dependent pattern of lymphocyte proliferation response and secreted gamma interferon and interleukin-2 when stimulated with irradiated R. tsutsugamushi Boryong, which is a cytokine profile of Th1 cells. High titers of antibody to R. tsutsugamushi were also demonstrated by indirect immunofluorescent-antibody testing. These findings suggest that the 56-kDa protein of R. tsutsugamushi is one of the candidates for a vaccine against scrub typhus.
The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its
in vivo
potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on
Gamma,
Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against
Gamma,
Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with
Gamma
and Delta variants substantiated
in vivo
potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against
Gamma
and Delta variants infection, hinting that CT-P59 has therapeutic
potential
for patients infected with
Gamma,
Delta and its associated variants.
SummaryAlthough chemotherapy remains among the best treatment options for most cancers, adjuvant therapies such as dendritic cell (DC)-based immunotherapy have been added to treatment protocols to destroy residual tumour cells. Combination treatment with low-dose temozolomide (TMZ) chemotherapy followed by vaccination with TAT-survivin-pulsed DCs enhanced T-cell responses specific for survivin and improved survival rate, as compared with DC alone or TMZ alone. Moreover, antigen-specific immunity appears to be mediated by CD8 + T cells, as determined by in vitro T-cell subset depletion. These studies demonstrated that a combination of low-dose TMZ chemotherapy and TAT-based DC immunotherapy may be a novel strategy for safe and effective treatment of malignant gliomas.
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