The modulation of MiR-155 and MiR-23a manipulates Klebsiella pneumoniae Adhesion on Human pulmonary Epithelial cells via Integrin α5β1 Signaling

Abstract

Micro-RNAs (miRNAs) critically regulate several host defense mechanisms, but their roles in the bacteria-epithelium interplay remain unclear. Our results displayed that the expression of miR-155 and miR-23a were down-regulated in K. pneumoniae-infected pulmonary epithelial cells. The elevated bacterial adhesion on A549 cells followed the enhancement of the cellular levels of these two miRNAs. Meanwhile, a mechanistic study demonstrated that miR-155 promoted integrin α5β1 function and resulted in the increased actin polymerization. Moreover, a non-histone nuclear protein, high mobility group nucleosomal-binding domain 2 (HMGN2) served as the potential target of miR-155 and miR-23a to regulate the integrin α5β1 expression and K. pneumoniae adhesion. Furthermore, the expression of a known integrin transcription suppressor-Nuclear Factor-I (NFI) was also repressed by miR-155, which paralleled with its chromatin location in the promoter regions of integrin α5 and β1. These results uncover novel links between miRNAs and integrin function to regulate bacterial adhesion, indicating a potential mechanism of host cell autonomous immune response to K. pneumoniae infection.

HMGN2 regulates non‐tuberculous mycobacteria survival via modulation of M1 macrophage polarization

“…For instance, we found that knock‐down of HMGN2 increases the internalization of Klebsiella pneumoniae into respiratory epithelial cells through the regulation of α5β1 integrin expression . HMGN2 involves in the miR‐155‐ and miR‐23a‐mediated manipulation of Klebsiella pneumoniae adhesion on human pulmonary epithelial cells . Our previous studies have mainly focused on the role of HMGN2 in epithelial cell function.…”

The Clinical Application of MicroRNAs in Infectious Disease

“…Cells isolated from patients infected with viral, fungal, and bacterial infections have different miRNA expression profiles compared with healthy controls, and this is also the case for infected versus non-infected cells in vitro ( 27 , 57 – 62 ). miRNA regulation has been described in a wide range of leukocytes and in the innate immune responses of non-leukocytes ( 12 , 34 , 63 – 71 ). Indeed, single nucleotide polymorphisms in miRNA loci have been associated with susceptibility to leprosy and infection outcome in human cytomegalovirus (hCMV) and hepatitis B infection ( 72 – 76 ).…”

Non-histone nuclear protein HMGN2 differently regulates the urothelium barrier function by altering expression of antimicrobial peptides and tight junction protein genes in UPEC J96-infected bladder epithelial cell monolayer

“…Recently, we found that the expression of HMGN2 was elevated in K. pneumoniae infected A549 and HBE 16 cells (Teng et al, 2016). To investigate whether HMGN2 is associated with UPEC infection in BECs, an acute bacterial cystitis in mice model was established by transurethral infection of UPEC J96 strain.…”