@article{HeinemannStalpBonifacioetal.2023,
  author    = {Heinemann, Anna Sophie and Stalp, Jan Lennart and Bonifacio, Jo{\~a}o Pedro Pereira and Silva, Filo and Willers, Maike and Heckmann, Julia and Fehlhaber, Beate and V{\"o}llger, Lena and Raafat, Dina and Normann, Nicole and Klos, Andreas and Hansen, Gesine and Schmolke, Mirco and Viemann, Dorothee},
  title     = {Silent neonatal influenza A virus infection primes systemic antimicrobial immunity},
  series = {Frontiers in Immunology},
  volume    = {14},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2023.1072142},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304782},
  year      = {2023},
  abstract  = {Infections with influenza A viruses (IAV) cause seasonal epidemics and global pandemics. The majority of these infections remain asymptomatic, especially among children below five years of age. Importantly, this is a time, when immunological imprinting takes place. Whether early-life infections with IAV affect the development of antimicrobial immunity is unknown. Using a preclinical mouse model, we demonstrate here that silent neonatal influenza infections have a remote beneficial impact on the later control of systemic juvenile-onset and adult-onset infections with an unrelated pathogen, Staphylococcus aureus, due to improved pathogen clearance and clinical resolution. Strategic vaccination with a live attenuated IAV vaccine elicited a similar protection phenotype. Mechanistically, the IAV priming effect primarily targets antimicrobial functions of the developing innate immune system including increased antimicrobial plasma activity and enhanced phagocyte functions and antigen-presenting properties at mucosal sites. Our results suggest a long-term benefit from an exposure to IAV during the neonatal phase, which might be exploited by strategic vaccination against influenza early in life to enforce the host's resistance to later bacterial infections.},
  language  = {en}
}
@article{KuschBornscheinLorethetal.2018,
  author    = {Kusch, Valentin and Bornschein, Grit and Loreth, Desiree and Bank, Julia and Jordan, Johannes and Baur, David and Watanabe, Masahiko and Kulik, Akos and Heckmann, Manfred and Eilers, Jens and Schmidt, Hartmut},
  title     = {Munc13-3 Is Required for the Developmental Localization of Ca2+ Channels to Active Zones and the Nanopositioning of Cav2.1 Near Release Sensors},
  series = {Cell Reports},
  volume    = {22},
  journal   = {Cell Reports},
  doi       = {10.1016/j.celrep.2018.02.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233468},
  pages     = {1965-1973},
  year      = {2018},
  abstract  = {Spatial relationships between Cav channels and release sensors at active zones (AZs) are a major determinant of synaptic fidelity. They are regulated developmentally, but the underlying molecular mechanisms are largely unclear. Here, we show that Munc13-3 regulates the density of Cav2.1 and Cav2.2 channels, alters the localization of Cav2.1, and is required for the development of tight, nanodomain coupling at parallel-fiber AZs. We combined EGTA application and Ca2+-channel pharmacology in electrophysiological and two-photon Ca2+ imaging experiments with quantitative freeze-fracture immunoelectron microscopy and mathematical modeling. We found that a normally occurring developmental shift from release being dominated by Ca2+ influx through Cav2.1 and Cav2.2 channels with domain overlap and loose coupling (microdomains) to a nanodomain Cav2.1 to sensor coupling is impaired in Munc13-3-deficient synapses. Thus, at AZs lacking Munc13-3, release remained triggered by Cav2.1 and Cav2.2 microdomains, suggesting a critical role of Munc13-3 in the formation of release sites with calcium channel nanodomains.},
  language  = {en}
}