Seong Kug Eo, Jin Hyoung Kim, Ajit Mahadev Patil, Jin Young Choi, Seong Bum Kim and Erdenebileg Uyangaa
Chonbuk National University, South Korea
Posters & Accepted Abstracts: J Clin Cell Immunol
Type I interferon (IFN-I)-dependent orchestrated mobilization of innate cells in inflamed tissues is believed to play a critical role in controlling replication and CNS-invasion of herpes simplex virus (HSV). However, the crucial regulators and cell populations that are affected by IFN-I to establish the early environment of innate cells in HSV-infected mucosal tissues are largely unknown. Here, we found that IFN-I signaling promoted the differentiation of CCL2-producing Ly-6Chi monocytes and IFN-Ã?Â³/granzyme B-producing NK cells, whereas deficiency of IFN-I signaling induced Ly-6Clo monocytes producing CXCL1 and CXCL2. More interestingly, recruitment of Ly-6Chi monocytes preceded that of NK cells with the levels peaked at 24 h post-infection in IFN-IÃ¢Â?Â?dependent manner, which was kinetically associated with the CCL2-CCL3 cascade response. Early Ly-6Chi monocyte recruitment was governed by CCL2 produced from hematopoietic stem cell (HSC)-derived leukocytes, whereas NK cell recruitment predominantly depended on CC chemokines produced by resident epithelial cells. Also, IFN-I signaling in HSC-derived leukocytes appeared to suppress Ly-6Ghi neutrophil recruitment to ameliorate immunopathology. Finally, tissue resident CD11bhiF4/80hi macrophages and CD11chiEpCAM+ dendritic cells appeared to produce initial CCL2 for migration-based self-amplification of early infiltrated Ly-6Chi monocytes upon stimulation by IFN-I produced from infected epithelial cells. Ultimately, these results decipher a detailed IFN-I-dependent pathway that establishes orchestrated mobilization of Ly-6Chi monocytes and NK cells through CCL2-CCL3 cascade response of HSC-derived leukocytes and epithelium-resident cells. Therefore, this cascade response of resident-to-hematopoietic-to-resident cells that drives cytokine-to-chemokine-to-cytokine production to recruit orchestrated innate cells is critical for attenuation of HSV replication in inflamed tissues.
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. They have got many reports to unveil how immune system works on viral encephalitis caused by Japanese encephalitis virus (J. Neuroinflammation, 2014 and 2016).