Professional Education


  • Doctor of Philosophy, Hannover Medical School-TWINCORE Centre for Experimental and Clinical Infection Research (Germany), Immunology and infection biology (2019)
  • Master of Science, University of Milan (Italy) (2014)
  • Bachelor of Science, University of Modena and Reggio Emilia (Italy) (2012)

Stanford Advisors


All Publications


  • Sequential MAVS and MyD88/TRIF signaling triggers anti-viral responses of tick-borne encephalitis virus-infected murine astrocytes JOURNAL OF NEUROSCIENCE RESEARCH Ghita, L., Breitkopf, V., Mulenge, F., Pavlou, A., Gern, O., Duran, V., Prajeeth, C., Kohls, M., Jung, K., Stangel, M., Steffen, I., Kalinke, U. 2021

    Abstract

    Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is typically transmitted upon tick bite and can cause meningitis and encephalitis in humans. In TBEV-infected mice, mitochondrial antiviral-signaling protein (MAVS), the downstream adaptor of retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) signaling, is needed to induce early type I interferon (IFN) responses and to confer protection. To characterize the brain-resident cell subset that produces protective IFN-β in TBEV-infected mice, we isolated neurons, astrocytes, and microglia from mice and exposed these cell types to TBEV in vitro. Under such conditions, neurons showed the highest percentage of infected cells, whereas astrocytes and microglia were infected to a lesser extent. In the supernatant (SN) of infected neurons, IFN-β was not detectable, while infected astrocytes showed high and microglia low IFN-β expression. Transcriptome analyses of astrocytes implied that MAVS signaling was needed early after TBEV infection. Accordingly, MAVS-deficient astrocytes showed enhanced TBEV infection and significantly reduced early IFN-β responses. Nevertheless, at later time points, moderate amounts of IFN-β were detected in the SN of infected MAVS-deficient astrocytes. Transcriptome analyses indicated that MAVS deficiency negatively affected the induction of early anti-viral responses, which resulted in significantly increased TBEV replication. Treatment with MyD88 and TRIF inhibiting peptides reduced only late IFN-β responses of TBEV-infected WT astrocytes and blocked entirely IFN-β responses of infected MAVS-deficient astrocytes. Thus, upon TBEV exposure of brain-resident cells, astrocytes are important IFN-β producers showing biphasic IFN-β induction that initially depends on MAVS and later on MyD88/TRIF signaling.

    View details for DOI 10.1002/jnr.24923

    View details for Web of Science ID 000676133300001

    View details for PubMedID 34296786

  • MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS. Science immunology Ghita, L., Spanier, J., Chhatbar, C., Mulenge, F., Pavlou, A., Larsen, P. K., Waltl, I., Lueder, Y., Kohls, M., Jung, K., Best, S. M., Förster, R., Stangel, M., Schreiner, D., Kalinke, U. 2021; 6 (60)

    Abstract

    Viral encephalitis initiates a series of immunological events in the brain that can lead to brain damage and death. Astrocytes express IFN-β in response to neurotropic infection, whereas activated microglia produce proinflammatory cytokines and accumulate at sites of infection. Here, we observed that neurotropic vesicular stomatitis virus (VSV) infection causes recruitment of leukocytes into the central nervous system (CNS), which requires MyD88, an adaptor of Toll-like receptor and interleukin-1 receptor signaling. Infiltrating leukocytes, and in particular CD8+ T cells, protected against lethal VSV infection of the CNS. Reconstitution of MyD88, specifically in neurons, restored chemokine production in the olfactory bulb as well as leukocyte recruitment into the infected CNS and enhanced survival. Comparative analysis of the translatome of neurons and astrocytes verified neurons as the critical source of chemokines, which regulated leukocyte infiltration of the infected brain and affected survival.

    View details for DOI 10.1126/sciimmunol.abc9165

    View details for PubMedID 34172587