Activation of TLRs/NF - κ B signal pathway and occurrence of different functionalcytokines during invasive pulmonary aspergillosis

Abstract

Objective To study the activation of TLRs/NF-κBsignal pathway and production of different functional cytokines during invasive pulmonaryaspergillosis( IPA) , in order to probe the pathogene-sis of IPA. Methods Mouse wererandomly divided into normal, normal + inoculated with Aspergillus fumigatus( normalinoculation group), and immune suppression + inoculation with Aspergillus fumigatus(IPAmodel group) , the mouse were killed at different time points after inhalingAspergillus fumigatus spores by nose. Removing the lung tissue in a sterile manner andmaking pathological section respectively, counting Aspergillus fumigatus colony,dynamiclly detecting the expression of TLR2, TLR4 mRNA, variation of NF-κB p65protein, pro-inflammatory cytokines TNF-α, IL-1β and anti-inflammatory cytokines IL-10 levels in the lung tissue byRT-PCR and Western blot method during Aspergillus fumigatus infection in mouse. Results(1) When it's 72 h after inhaling Aspergillus fumigatus by nose, IPA model emerged severelung tissue inflammation, and generated a large number of hyphae, meanwhile, burthen ofAspergillus fumigatus was higher than normal inoculation group at each time point.(2)Compared with the normal inoculation group, IPA group whose TLR2 mRNA was lowexpression at early stage of infection (24 h), and emerged high expression at late stageof infection (120 h, 144 h); and TLR4 mRNA has been at a state of low expression in theinfection process; NF-κB p65 suddenly increased at early stage ofinfection(24 h) and then continued to decline. (3) After infected by Aspergillus fumigatusin normal mouse, proinflammatory cytokine TNF-α, IL-1β in lung exhibited high expression at the early stages of infection,and the highest expression levels appeared at 48 h or 72 h, then decreased and recoveredto normal level. And the expression level of anti-inflammatory cytokine IL-10 rised atlate stage of infection; The IP A mouse released a lot of anti-inflammatory cytokine IL-10at early stage of infection, which significantly reduced at late stage, and releasedpro-inflammatory cyto-kines TNF-α, IL-1β at slow and low level. Conclusion The abnormal activation ofTLRs/NF-β signaling pathway caused the loss of dynamic balance between pro-inflammatorycytokines and anti-inflammatory cytokines, leading to the occurrence and development ofIPA.