Selection of Listeria monocytogenes InlA-Binding Peptides Using Phage Display—Novel Compounds for Diagnostic Applications?

Listeria monocytogenes is a pathogenic, gram-positive bacterium causing foodborne infections and listeriosis, an infection responsible for serious medical conditions, especially for pregnant women, newborns, or people with a weak immune system. Even after antibiotic treatment, 30% of clinical infections result in death. L. monocytogenes is able to enter and multiply in mammalian cells. Invasion into epithelial cells in the human intestine is mediated by the interaction of the bacterial surface protein internalin A (InlA) with the host cell receptor E-cadherin (E-cad). We have used phage display to select InlA-specific peptides consisting of 12 amino acids using a randomized, recombinant peptide library. We could demonstrate that the selected peptides bound to recombinant InlA protein as well as to L. monocytogenes cells. In vitro, some of the peptides inhibited the interaction between recombinant InlA and human E-cad. As far as we know, this is the first publication on the development of InlA-specific peptide ligands. In the future, our peptides might be used for the development of innovative diagnostic tools or even therapeutic approaches

Insulin Modulates the Inflammatory Granulocyte Response to Streptococci via Phosphatidylinositol 3-Kinase

Group B streptococci (GBS; Streptococcus agalactiae) are a major cause of invasive infections in newborn infants and in patients with type 2 diabetes. Both patient groups exhibit peripheral insulin resistance and alterations in polymorphonuclear leukocyte (PML) function. In this investigation, we studied the PML response repertoire to GBS with a focus on TLR signaling and the modulation of this response by insulin in mice and humans. We found that GBS-induced, MyD88-dependent chemokine formation of PML was specifically downmodulated by insulin via insulin receptor-mediated induction of PI3K. PI3K inhibited transcription of chemokine genes on the level of NF-kappa B activation and binding. Insulin specifically modulated the chemokine response of PML to whole bacteria, but affected neither activation by purified TLR agonists nor antimicrobial properties, such as migration, phagocytosis, bacterial killing, and formation of reactive oxygen species. The targeted modulation of bacteria-induced chemokine formation by insulin via PI3K may form a basis for the development of novel targets of adjunctive sepsis therapy. The Journal of Immunology, 2012, 189: 4582-459

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Background: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. Objective: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. Methods: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. Results: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. Conclusions: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations. (J Allergy Clin Immunol 2021;148:1332-41.