Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation.

Hepatitis B virus (HBV) is a major driver of chronic hepatic inflammation, which regularly leads to liver cirrhosis or hepatocellular carcinoma. Immediate innate immune cell response is crucial for the rapid clearance of the infection. Here, natural killer (NK) cells play a pivotal role in direct cytotoxicity and the secretion of antiviral cytokines as well as regulatory function. The aim of this study was to further elucidate NK cell responses triggered by an HBV infection. Therefore, we optimized HBV in vitro models that reliably stimulate NK cells using hepatocyte-like HepG2 cells expressing the Na+-taurocholate co-transporting polypeptide (NTCP) and HepaRG cells. Immune cells were acquired from healthy platelet donors. Initially, HepG2-NTCP cells demonstrated higher viral replication compared to HepaRG cells. Co-cultures with immune cells revealed increased production of interferon-γ and tumor necrosis factor-α by NK cells, which was no longer evident in isolated NK cells. Likewise, the depletion of monocytes and spatial separation from target cells led to the absence of the antiviral cytokine production of NK cells. Eventually, the combined co-culture of isolated NK cells and monocytes led to a sufficient cytokine response of NK cells, which was also apparent when communication between the two immune cell subpopulations was restricted to soluble factors. In summary, our study demonstrates antiviral cytokine production by NK cells in response to HBV+ HepG2-NTCP cells, which is dependent on monocyte bystander activation.

[OPD in the hospital: an algorithm for structuring the diagnostic process with the Operationalized Psychodynamic Diagnostics OPD-2]. / OPD in der klinik: ein algorithmus für die therapieplanung mit der Operationalisierten Psychodynamischen Diagnostik (OPD-2).

OBJECTIVES: Operationalized psychodynamic diagnostics OPD-2 is a diagnostic procedure that has proven to be valuable for psychotherapy. However, to date there has been only little discussion about the application context and any necessary adaptations to various clinical fields. METHODS AND RESULTS: The working group "Implementation of OPD in Clinical Practice" proposes an algorithm for the sequential and adapted use of OPD depending on the clinical context. CONCLUSION: Especially for patients who are primarily not open to receiving psychotherapy, e.g., in psychiatric hospitals or general hospitals, OPD can be an important basis for structuring motivating interventions. A stepwise procedure is proposed which is adapted to the usage of OPD in such contexts. Furthermore, also for these contexts, simplified ratings are proposed and discussed for the axes relationships, conflicts and structure. However, complete OPD remains recommended when determining the focus of a psychotherapeutic treatment.