Infection and Immunity Introduction Infection Immunity is the studies of host-pathogen interactions. After infection, pathogens activate immune recognition system and innate immune signaling, which further induces the adaptive immune responses. The human innate and adaptive immune systems function to defeat pathogens. However, pathogens have evolved strategies to evade the human immune regulatory mechanisms for their own propagation. We are studying some pathogens including coxsackievirus B3 (CVB3), hepatitis B virus (HBV), M. tuberculosis, HSV-1, and Flaviviruses, and focusing on the following scientific questions: (1) pathogens mediated immune recognition and immune response; (2) immunopathological mechanisms induced by pathogens and prevention/therapy strategies; (3) immunoregulation mechanisms induced by pathogen infections; (4) immune evasion mechanisms of pathogens. Through these efforts, we may provide better understanding of pathogenesis mechanisms of infectious disease as well as effective treatments. Our focus 1. Pathogens mediated immune recognition and immune response (1) Immune recognition and immune regulation in CVB3-induced myocarditis and TB. We focus on coxsackievirus B3 (CVB3) induced viral myocarditis, hepatitis B virus (HBV) and M. tuberculosis infection, which still remain major public health problems to be resolved in the country. (2) Exploration of novel innate sensors for microbe (CVB3 and M.tb) We propose that innate sensors may attribute to the recognition of CVB3 not only in the heart, but also in the context of intestine, which is the primary entry site for CVB3 infection. By means of high-throughput screening technologies, we try to detect the expression profiles of all TLRs and cytosolic/endosomal RNA sensors following CVB3 infection, and focus on novel sensors identification, its role on the proinflammatory cytokines production as well as viral inhibition and the signaling pathway they may activate. Triggering receptor expressed on myeloid cells (TREM), a novel innate immune receptors mainly expressed on neutrophils, monocytes, macrophages and dendritic cells, is reported to play critical roles in fine-tuning the inflammatory response. We hypothesize that TREM2 serves as an important innate sensor for M.tb considering its high expression level on alveolar macrophages and its inflammation-modulatory function. The murine TB model and the in vitro macrophage cell-culture model are utilized to explore the expression dynamics, the bacterial-binding and phagocytosis ability as well as the inflammation-regulatory function of TREM2 following M.tb infection; and hope to definite the key role of TREM2 in tuberculosis. 2. Immunopathological mechanisms induced by pathogens and prevention/therapy strategies (1) Immunopathological mechanisms and therapeutic strategies of coxsackievirus B3 (CVB3) induced myocarditis and tuberculosis. Following CVB3 infection, endoplasmic reticulum stress was activated in myocardiocytes and promote the production of chemokines and cytokines, which recruits circulating leukocytes from blood vessels into myocardial tissue and drive macrophage polarized into proinflammatory M1 phenotype in male mice and anti-inflammatory M2a phenotype in females. This sexually differential polarization of macrophages further cause the diverse bias of T cell immune response and lead to the distinct gender bias in CVB3-induced myocarditis. (2) Molecular design of novel vaccines against infectious disease To guarantee the effective immunization of gene vaccine via mucosal site, Chitosan, a cationic polysaccharides has been used by us as a proper delivery system to circumvent mucosal fast-antigen degradation, to promote mucosal permeability therefore enhancing the uptake of DNA by mucus epithelial cells and M-cells and for sustained release of Ags. We have successfully used chitosan-pVP1 vaccine to induce mucosal immunity which provided enhanced prevention against CVB3–myocarditis. chitosan and oligo-chitosan are utilized to encapsulate TB gene vaccine to provoke mucosal immune response. 3. Immunoregulation mechanisms induced by pathogen infections (1) Cytokine-mediated anti-viral immune signaling We are focusing on studying the roles of protein ubiquitination and deubiquitination in regulating IFNs mediated antiviral signaling. It includes: (1) the role of E3s/DUBs in regulating IFNs-mediated antiviral signaling cascades; (2) the role of E3s/DUBs in regulating the level of IFNs-stimulated genes (ISGs); (3) the role of E3s/DUBs in regulating viral evasion of IFNs-mediated antiviral signaling. (2) Vector-borne infectious diseases To study the interaction between “tick-pathogen and host” is the key step for understanding the mechanism of transmission and pathogenesis of tick-borne diseases. Most researches right now are focused on the interaction between pathogen and human immune system; while the interaction between pathogen and insect vector is also important. As the effective intermediate host for numerous pathogens, ticks have unique immune systems to combat the infection; while the pathogens develop strategy to adapt to the tick immune system. We mainly focus on the following aspects：pathogen-host interaction in vector-borne diseases，infection and pathogenesis of Flaviviruses，new vaccine strategy against vector-borne diseases. |