Type III secretion system of Pseudomonas aeruginosa affects mucin gene expression via NF-κB and AKT signaling in human carcinoma epithelial cells and a pneumonia mouse model
Abstract
The type III secretion system (T3SS) in Pseudomonas aeruginosa has been linked to severe disease and poor clinical outcomes in animal and human studies. Of the various T3SS effector genes, ExoS and ExoT showed mutually exclusive distributions, and these two genes showed varied virulence. We aimed to investigate whether the ExoS and ExoT effector proteins of P. aeruginosa affect the expression of the proinflammatory mediators Muc7, Muc13, Muc15, and Muc19 via the NF-κB and AKT signaling pathways. To understand the role of the T3SS, we used AExoS, AExoT, and T3SS transcriptional activator ExsA mutants (ExsA∷Ω), as well as A549 cells stimulated with P. aeruginosa strain K (PAK). We investigated the effects of ΔExoS, ΔExoT, and ExsA∷Ω on the development of pneumonia in a mouse model and on Muc7, Muc13, Muc15, and Muc19 production in A549 cells. ΔExoS and ΔExoT markedly decreased the neutrophil count in the bronchoalveolar lavage fluid, with a reduction in Muc7, Muc13, Muc15, and Muc19 expression ΔExoS andΔExoT reduced NF-κB and AKT phosphorylation, together with Muc7, Muc13, Muc15, and Muc19 expression in PAK-infected mice and A549 cells. In conclusion, P. aeruginosa infection induced the expression of Mucus, and the P. aeruginosa T3SS appeared to be a key player in Muc7, Muc13, Muc15, and Muc19 expression, which is further controlled by NF-κB and AKT signaling. These findings might be useful to devise a novel therapeutic approach for the treatment of chronic pulmonary…
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