Previously, a dominant role of the adaptive immune system in the pathogenesis of Sjögren's syndrome was suspected. Recent advances, however, have revealed a major role of the type I IFN pathway, documented by an increased circulating type I IFN activity and an IFN 'signature' in peripheral blood mononuclear cells and minor salivary gland biopsies from the patients. Polymorphisms in the genes IRF5 and STAT4 leading to increased IFN activation are associated with disease susceptibility. In the pathogenesis of Sjögren's syndrome, the activation of salivary gland epithelial cells appears to be the initial event. Once intrinsically activated, they express costimulatory and Toll-like receptors (TLRs) and MHC class I and II molecules, can present autoantigens and produce proinflammatory cytokines. The subsequent activation of plasmacytoid dendritic cells induces the production of high levels of proinflammatory cytokines in individuals with the risk alleles of the susceptibility genes IRF5 and STAT4. Under the influence of the high IFN concentration in the glands and through TLR ligation, B-cell activating factor is produced by epithelial cells and, together with autoantigen presentation on salivary gland epithelial cells, stimulates the adaptive immune system. In view of the central role of IFNalpha in at least the initiation of the pathogenesis of Sjögren's syndrome, blockade of this cytokine may be a rational therapeutic approach.

LILRA3 is the sole soluble member of the LILR family. Previous studies from our group had shown that a 6.7 kb genetic deletion of LILRA3 is associated with MS and Sjögren’s syndrome. An impairment of the immune response leads to a predisposition for B-NHL, so we wanted to study whether the deletion of LILRA3 is also a risk factor for B-NHL, as well as the function of LILRA3. We discovered that the frequency of the homozygous LILRA3 deletion was significantly higher in B-NHL (6%) than in blood donors (3%) (P = 0.03). We detected binding of fluorochrome-conjugated recombinant LILRA3 to monocytes and B-cells. Incubation of PBMCs with recombinant LILRA3 induced proliferation of CD8⁺ T-cells and NK cells, as determined by CFSE staining. Using a transwell system, we demonstrated that LILRA3-stimulated lymphocyte proliferation was mediated by monocytes and required both cell contact and soluble factors. Secretion of IL-6, IL-8, IL-1β and IL-10 in the cell supernatant was stimulated by LILRA3. We conclude that LILRA3 is an immunostimulatory molecule, whose deficiency is associated with higher frequency of B-NHL.

LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context of HIV infection. We analyzed a panel of TLR agonists and found that ssRNA40, a TLR8 agonist, is a potent inducer of LILRA3 in healthy individuals. However, this regulation is much diminished in HIV. Comparison of TLR8 to TLR4 induction of LILRA3 indicated that LPS induces less LILRA3 than ssRNA40 among healthy controls, but not HIV patients. Levels of LILRA3 induction correlated to virus load and CD4 counts in untreated patients. Recombinant LILRA3 can induce a host of proinflammatory genes which include IL-6 and IL-1α, as well as alter the expression of MHC and costimulatory molecules in monocytes and B-cells. Our experiments point towards a beneficial role for LILRA3 in virus infections, especially in ssRNA viruses, like HIV, that engage TLR8. However, the potentially beneficial role of LILRA3 is abrogated during a HIV infection. We believe that more work has to be done to study the role of LILRA3 in infectious diseases and that there is a potential for exploring the use of LILRA3 in the treatment of virus infections.

The genus Weissella and the recently described genus Periweissella, to which some previously named Weissella species have been reclassified as a result of a taxogenomic assessment, includes lactic acid bacteria species with high biotechnological and probiotic potential. Only one species, namely, Periweissella (P.) beninensis, whose type strain has been shown to possess probiotic features, has so far been described to be motile. However, the availability of numerous genome sequences of Weissella and Periweissella species prompted the possibility to screen for the presence of the genetic determinants encoding motility in Weissella and Periweissellas spp. other than P. beninensis. Herein, we performed a comprehensive genomic analysis to identify motility-related proteins in all Weissella and Periweissella species described so far, and extended the analysis to the recently sequenced Lactobacillaceae spp. Furthermore, we performed motility assays and transmission electron microscopy (TEM) on Periweissella type strains to confirm the genomic prediction. The homology-based analysis revealed genes coding for motility proteins only in the type strains of P. beninensis, P. fabalis, P. fabaria and P. ghanensis genomes. However, only the P. beninensis type strain was positive in the motility assay and displayed run-and-tumble behavior. Many peritrichous and long flagella on bacterial cells were visualized via TEM, as well. As for the Lactobacillaceae, in addition to the species previously described to harbor motility proteins, the genetic determinants of motility were also found in the genomes of the type strains of Lactobacillus rogosae and Ligilactobacillus salitolerans. This study, which is one of the first to analyze the genomes of Weissella, Periweissella and the recently sequenced Lactobacillaceae spp. for the presence of genes coding for motility proteins and which assesses the associated motility phenotypes, provides novel results that expand knowledge on these genera and are useful in the further characterization of lactic acid bacteria.

Foodborne bacterial pathogens continue to pose a significant global health and economic burden, with Listeria monocytogenes being a persistent risk due to its frequent involvement in outbreaks and food recalls. Bacteriophage-based products are promising tools for enhancing food safety, yet systematic evaluations across genetically diverse L. monocytogenes strains are limited. In this study, we assessed the efficacy of a commercially available Listeria-specific phage product against 50 whole-genome-sequenced clinical and food-associated L. monocytogenes isolates recently collected in Germany. Traditional spot and plaque assays indicated 70–76% susceptibility, whereas viability-based methods, including colony reduction, OD₆₀₀ measurement, and flow cytometry, demonstrated substantial bacterial reduction across all isolates within 24 h. Notably, flow cytometry revealed a marked decline in viable cells as early as 3 h post-treatment. By systematically comparing susceptibility assays, we argue that modern viability-based methods assessing microbial load reduction offer key advantages over classical plaque assays for evaluating phage efficacy in food safety applications. While plaque assays remain valuable primarily for determining infectivity, reduction-based approaches have the potential to serve as a measure of antimicrobial performance in biocontrol settings.

• Most mutations occurred in genes associated with WTA glycosylation. • All mutants exhibited impaired P100 phage binding. • Gene mutation patterns appeared serovar-dependent. • Serovar 4b-derived mutants showed greater fitness loss than 2a or 2b. • Phage-resistance induction led to increased antibiotics sensitivity.