Expression Of Dectin-1is Regulated By TLR2and Transcriptional Factor PU.1during Aspergillus Fumigatus Infection

Recently，with the increase of the susceptible population，the incidence of infection ofAspergillus fumigatus presents a rising trend．Even more effective antifungal agents beingused on clinical，and the level of clinical diagnosis and treatment constantly improving，themortality rate of invasive aspergillosis（IA） is still as high as50%～90%．Studies haveshown the immune defense of host plays a key role against aspergillosis，but little is knownabout the regulation and mechanism involved in this defense．Scince the mechanism ofAspergillus fumigatus infection host has been revealed，people have recognized that thecombination of pattern recognition receptors（PRRs） and pathogen-associated molecularpatterns（PAMP） is the beginning of anti-fungal immunity．The role，the PRRs plays inimmune system，has got increasing attention and this provides the possibility to find newideas of aspergillosis prevention through host immune state intervention．In antifungal immunity，Dectin-1receptor is considered as the main PRRs．Dectin-1receptor，belonging to C-type plant lectin family，is a type II transmembrane receptor．byidentifying β-(1，3) glucan Dectin-1receptor can mediate host antifungal immune defenseresponse，including phagocytose，respiratory burst and generates a large number of cellchemokine，such as TNF，IL-1，GM-CSF．Researches focusing on the expression andregulation of Dectin-1receptor are needed，which is very important in the control of IA．Inthis research，by establishing vitro model of Aspergillus fumigatus infection，we observedDectin-1receptor expression in Aspergillus fumigatus infection changes as Toll-like receptor2（TLR2）， transcription factor PU.1silenced through siRNA technology．Part I the role TLR2plays in expression of Dectin-1receptor in HBEcells exposed to Aspergillus fumigatesObjective：Through establishing vitro model of HBE cells exposedto Aspergillusfumigates，we intend to observe the expression of Dectin-1receptor and TLR2cells and therelationship between them．Methods：HBE cells are incubated with Aspergillus fumigatesconidia (MOI=1)．The expression of Dectin-1，TLR2are detected by PCR，Western Blot. TLR2is silenced by siRNA to observe the changes of Dectin-1expression．Results:Stimulated by Aspergillus fumigates，the expression of Dectin-1mRNA is stronger6h laterand reaches the peak after24hours，whereas TLR2just maintain high level of expression.TLR2silenced，the expression of Dectin-1significantly decreased in HBE cells duringinfection. Conclusion: Our findings demonstrate the expression of Dectin-1、TLR2getstronger as HBE cells exposed to Aspergillus fumigates．In addition，and the induction ofDectin-1of HBE cells is related to TLR2．Part II the role transcription factor PU.1plays in the expression ofDectin-1receptor when macrophage cells are exposed to AspergillusfumigatesObjective：To observe the influencing factor of Dectin-1expression when macrophagecells are exposed to Aspergillus fumigates by transcriptional level. Methods：PU.1issilencedby siRNA to observe the changes of Dectin-1expression and the ability of phagocytose ofTHP-1drived macrophage cells challenged by Aspergillus fumigates．Results：Stumilated byAspergillus fumigates，the expression of PU.1is stronger6h later and reach the peak after24hours． PU.1silenced， the expression of Dectin-1in THP-1drived macrophage cellssignificantly decrease during infection. And the phagocytose ability of THP-1drivedmacrophage cells decrease as well．Conclusion：The expression of Dectin-1and theophagocytose ability of THP-1drived macrophage cells are related to PU.1some how.