euro-infectious-diseases-histopathology-2018-posters

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Notes:
Volume 4 Journal of Infectious Diseases and Treatment
ISSN: 2472-1093
Page 42
Euro Infectious Diseases 2018 &
Histopathology 2018
September 27-29, 2018
&
JOINT EVENT
September 27-29, 2018 Rome, Italy
5th International Conference on Histopathology & Cytopathology
10th Euro-Global Conference on Infectious Diseases
Blocking 4-1BB signal ameliorates the progression of Japanese encephalitis via divergent type I
innate responses
Seong Kug Eo, Seong Bum Kim, Jin Young Choi, Jin Hyoung Kim and Erdenebelig Uyangaa
Chonbuk National University, South Korea
Japanese encephalitis (JE), a neuroinflammation caused by zoonotic JE virus, is the major cause of viral encephalitis
worldwide and poses an increasing threat to global health and welfare. To date, however, there has been no report describing
the regulation of JE progression using immunomodulatory tools for developing therapeutic strategies. We tested whether
blocking the 4-1BB signaling pathway would regulate JE progression using murine JE model. Infected wild-type and 4-1BB-
knockout (KO) mice were examined daily for mortality and clinical signs and neuroinflammation in the CNS was evaluated
by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, JEV-specific T cell and type I/II
IFN (IFN-I/II) innate responses were analyzed. Blocking the 4-1BB signaling pathway significantly increased resistance to JE
and reduced viral burden in extraneural tissues and the CNS, rather than causing a detrimental effect. In addition, treatment
with 4-1BB agonistic antibody exacerbated JE. Furthermore, JE amelioration and reduction of viral burden by blocking the
4-1BB signaling pathways were associated with an increased frequency of IFN-II-producing NK and CD4+ Th1 cells as well as
increased infiltration of mature Ly-6Chi monocytes in the inflamed CNS. More interestingly, DCs and macrophages derived
from 4-1BB KO mice showed potent and rapid IFN-I innate immune responses upon JEV infection, which was coupled to
strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7) and antiviral ISG genes (ISG49, ISG54, ISG56). Further,
the ablation of 4-1BB signaling enhanced IFN-I innate responses in neuron cells, which likely regulated viral spread in the
CNS. Finally, we confirmed that blocking the 4-1BB signaling pathway in myeloid cells derived from hematopoietic stem cells
(HSCs) played a dominant role in ameliorating JE. In support of this finding, HSC-derived leukocytes played a dominant role
in generating the IFN-I innate responses in the host.
Biography
Seong Kug Eo’s lab has focused on unveiling how hosts response to pathogen infection. They have used various infectious models to prove host responses upon
pathogenic infection. In recent, EO’s lab has found the detailed pathway that IFN-I signal pathway orchestrated environments to provide effective protection against
mucosal viral infection (PLoS Pathog., 2016). Moreover, EO’s lab is expert on viral acute encephalitis caused by flaviviral infection.
Seong Kug Eo et al., J Infec Dis Treat 2018, Volume 4
DOI: 10.21767/2472-1093-C1-003