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The replication of viruses in secondary lymphoid organs guarantees sufficient amounts of pattern-recognition receptor ligands and antigens to activate the innate and adaptive immune system. Viruses with broad cell tropism usually replicate in lymphoid organs, however, whether a virus with a narrow tropism relies on replication in the secondary lymphoid organs to activate the immune system remains not well studied. In this study, we used the artificial intravenous route of infection to determine whether Influenza A virus (IAV) replication can occur in secondary lymphatic organs (SLO) and whether such replication correlates with innate immune activation. Indeed, we found that IAV replicates in secondary lymphatic tissue. IAV replication was dependent on the expression of Sialic acid residues in antigen-presenting cells and on the expression of the interferon-inhibitor UBP43 (Usp18). The replication of IAV correlated with innate immune activation, resulting in IAV eradication. The genetic deletion of Usp18 curbed IAV replication and limited innate immune activation. In conclusion, we found that IAV replicates in SLO, a mechanism which allows innate immune activation.

An unfamiliar looking azooxanthellate dendrophylliid coral, observed during shallow water (3-19 m) visual censuses since 2015 in Hispaniola and since 2019 in Puerto Rico, has been identified as Cladopsammia manuelensis sensu Cairns, 2000 (hereafter C. manuelensis). Genus assignment is based on morphological (e.g. large, widely separated and divergently oriented polyps that grow by extratentacular division, either near the base of another polyp or separated from others by a flattened coenenchyme) and genetic data (CO1 gene). We highlight the taxonomic uncertainty of the species affiliation of Cladopsammia manuelensis as well as the unresolved status of the closely related genera Cladopsammia, Rhizopsammia and Dendrophyllia. Typically found deeper (at 43-366 m) in the tropical-subtropical Atlantic Ocean and western Indian Ocean, C. manuelensis is also known to have increased in abundance in semi-cryptic habitats over the last decade at 4- 30 m in Curaçao and occurs in transects at 10 m in Aruba. The recent appearance of C. manuelensis at snorkel- SCUBA depths may represent an upward expansion of its bathymetric range and/or emergence from the cryptic habitats that abound on shallow reefs. Cladopsammia manuelensis superficially resembles, and genetically is relatively closely related to, three, highly invasive, semi-cryptic dendrophylliid Tubastraea species, and may show a similar ability to spread widely on tropical western Atlantic reefs.

Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (Itgae, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection. OA Förderung 2021

Dissertation, Universität Duisburg-Essen, 2020 (Kumulative Dissertation)

The replication of virus in secondary lymphoid organs is crucial for the activation of antigen-presenting cells. Balanced viral replication ensures the sufficient availability of antigens and production of cytokines, and both of which are needed for virus-specific immune activation and viral elimination. Host factors that regulate coordinated viral replication are not fully understood. In the study reported here, we identified Map3k14 as an important regulator of enforced viral replication in the spleen while performing genome-wide association studies of various inbred mouse lines in a model of lymphocytic choriomeningitis virus (LCMV) infection. When alymphoplasia mice (aly/aly, Map3k14aly/aly, or Nikaly/aly), which carry a mutation in Map3k14, were infected with LCMV or vesicular stomatitis virus (VSV), they display early reductions in early viral replication in the spleen, reduced innate and adaptive immune activation, and lack of viral control. Histologically, scant B cells and the lack of CD169+ macrophages correlated with reduced immune activation in Map3k14aly/aly mice. The transfer of wildtype B cells into Map3k14aly/aly mice repopulated CD169+ macrophages, restored enforced viral replication, and resulted in enhanced immune activation and faster viral control.

Einleitung: Durch medizintechnische, soziale sowie ökonomische Fortschritte stieg weltweit die Anzahl von älteren Menschen in der Bevölkerung in den letzten Jahrzehnten kontinuierlich an. Aufgrund einer höheren Sensibilisierung der Gesellschaft für Gewalterfahrungen Älterer rückte dieses Thema stärker in den Mittelpunkt des öffentlichen Interesses. Gerade hinsichtlich tödlicher Gewalt existieren jedoch bisher nur recht wenige Studien – in Deutschland fünf Arbeiten hinsichtlich der Städte Bonn, Hannover, Aachen, Hamburg und Essen, im Ausland vier Vergleichsstudien. Methodik: Es wurden retrospektiv 23.414 Obduktionsprotokolle im Hinblick auf Tötungsdelikte an über 60-Jährigen im Jahreszeitraum von 2000 bis 2010 des Instituts für Rechtsmedizin der Charité, der Freien Universität und der Humboldt Universität Berlin untersucht. Ausschlusskriterien waren stark fäulnisveränderte Leichen, unklare Todesfälle, Serientötungen, Tod durch unterlassene Hilfeleistung, ärztliche und pflegerische Kunstfehler, Euthanasie sowie versuchte Tötungsdelikte. Datenlage und Ergebnisse: Es fanden sich 93 Tötungsdelikte an älteren Menschen über 60 Jahren bei gesamt 480 Tötungsverbrechen an allen Altersklassen zwischen 2000 und 2010. Somit war der Anteil der über 60-Jährigen mit 19,4 % recht niedrig, er lag sogar unter dem Wohnbevölkerungsanteil dieser Altersklasse in Berlin (24,1 %). Die Staatsanwaltschaft ermöglichte Akteneinsicht in 73,1 % der Fälle (68 Akten), 55 Täter waren zum Zeitpunkt der Aktenauswertung bekannt. Auch wenn sich Unterschiede hinsichtlich der Altersgruppen und der Tötungsarten der Opfer ergeben hatten, fand sich ein fast identisches Viktimisierungsrisiko für Männer und Frauen ab 60 Jahren. Opfer und Täter der vorliegenden Studie können in spezielle Profilgruppen eingeteilt werden: Einerseits in die Gruppe der altersunabhängigen Tötungen aufgrund von Streitigkeiten meist unter alkoholischer Beeinflussung oder aufgrund von Erkrankungen des Täters, die zu einem Großteil dem psychiatrischen Formenkreis angehören. Zum anderen finden sich die altersabhängigen Tötungen, laut Schäfer (1989) auch „Gerontozide“ genannt: Raubüberfälle an älteren Frauen und Tötung mit dem Ziel der Erlösung von körperlichem Leiden der Opfer. In letzterem Falle begingen die meist ebenso über 60-jährigen Täter zu einem hohen Anteil Suizid nach dem Homizid. Schlussfolgerungen: Im Alter ist die Viktimisierungsgefahr eigentlich kleiner, da sich ältere Menschen weniger im öffentlichen Raum aufhalten. Es zeigt sich aber eine Verlegung der Gewalt in den privaten Raum, der der Öffentlichkeit nur schwer zugänglich ist. Dem könnte mit folgenden Lösungsansätzen begegnet werden: eine gestärkte Arzt-Patientenbeziehung mit Einbeziehung des sozialen Umfelds des Patienten, Behandlung von Depressionen und anderen psychiatrischen Erkrankungen, Schulungen des medizinischen Personals hinsichtlich physischer und psychischer Missbrauchssymptome Älterer, zugängliche Hilfsangebote für Betroffene, ausführlichere Leichenschauen sowie eine weitere Sensibilisierung der Öffentlichkeit zum Thema Gewalt an Älteren., Introduction: Medical and socioeconomic improvements have led during recent decades to a steady increase of elderly people in the world. Due to increased public sensitivity to the issue, violence against eldely people is nowadays more considered by society. There is still a lack of detailed information concerning deadly aggression – there are five German studies from Bonn, Hannover, Aachen, Hamburg and Essen and four studies from abroad compared in this study. Methods: In a retrospective study we examined 23.414 autopsy files of sexagenarians or older between 2000 and 2010 at the Charité Berlin (plus Humboldt and Free University before the association to Charité Berlin). We excluded cases with strong putridity, ambiguous deaths, serial killings, non- assistance of persons in danger, medical malpractice, euthanasia and attempted homicides. Data research and results: During this period a total of 93 homicides against people over 60 occurred in comparison with 480 fatal attacks against all age classes. This percentage (19,4 %) is even lower than that of the resident population of elderly people in Berlin (24,1 %). The department of public prosecution allowed access to 68 records (73,1 %). 55 perpetrators were known at the point of investigation. Even if there were differences in age classes and methods of killing for men and women, the victims of both genders over 60 had almost the same risk of being killed. The present study allows a classification of victims and perpetrators in special profile groups: on the one hand there are killings irrespective of the victims age due to disputes mostly under the influence of alcohol or due to the perpetrators having an (psychiatric) illness. On the other hand there are killings dependent on the victim`s age (“gerontocides”): armed robbery of old women and killings by close partners aimed at ending an insufferable disease. Many of these offenders were aged over 60 as well and committed suicide. Conclusions: The danger of victimization of elderly people is smaller because they act less in the public. But there is a considerable shift of violence in domestic areas. To prevent homicides the following points are important: a strong relationship between physician, patient and their social surroundings, the treatment of psychiatric illness, more detailed instruction of medical personal on the physical and mental symptoms of elderly abuse, good access to support services for those affected, detailed autopsies and a stronger sensibilization of the public violence against elderly people.