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Gene expression profiles of Siglec-14/THP-1 and Siglec-5/THP cell lines, with or without NTHi stimulation

ABSTRACT: Acquisition of a new strain of non-typeable Haemophilus influenzae (NTHi) is often associated with exacerbation of chronic obstructive pulmonary disease (COPD). We have previously reported that COPD patients who are homozygous null for SIGLEC14 gene is less susceptible to COPD exacerbation than those who have wild-type allele with functional SIGLEC14 gene. In order to gain insight into the mechanism behind the COPD exacerbation, and to find new clues that may lead to the discovery of objective biomarker of COPD exacerbation, Siglec-14/THP-1 and Siglec-5/THP-1 cell lines, which mimic monocytes from homozygous wild-type and homozygous SIGLEC14-null person, respectively, were incubated with or without NTHi, and their gene expression profiles were compared by using Affymetrix Human Genome U133 Plus 2.0 Array.

ORGANISM(S): Homo sapiens

PROVIDER: GSE47929 | GEO | 2014/08/04

SECONDARY ACCESSION(S): PRJNA208379

REPOSITORIES: GEO

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Project description:Objectives: Therapies being safe, effective and not vulnerable to develop resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by the use of host-directed drugs to counteract microbial infections. This study sought to identify cellular genes and pathways differentially expressed during airways epithelial infection by nontypable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). Based on the proposed relationship between NTHi intracellular location and persistence, the antimicrobial potential of a panel of drugs perturbing host pathways used by NTHi to enter epithelial cells was investigated. Methods: We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing A549 cell whole genome expression profiling, and identified a panel of host target candidates which were pharmacologically modulated. Interfering drugs were tested for their bactericidal effect, cytotoxicity, effect on the interplay NTHi-epithelial cell, and effect on NTHi respiratory infection in vivo, by assessing lung bacterial loads in a murine intranasal infection model. Results: The sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi; the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts both intracellularly and in the lungs of infected mice. Conclusions: PDE4 inhibition is currently prescribed in COPD; resveratrol is a geroprotector attractive for COPD treatment by preventing lung aging. This work provides evidence for the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection. Haemophilus influenzae clinical strain NTHi375 induced gene expression in A549 human type II pneumocyte cell line was measured at 2 h post-infection. Non infected cells were used as a control. Four independent experiments were performed for each condition.

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Gene expression profiles of Siglec-14/THP-1 and Siglec-5/THP cell lines, with or without NTHi stimulation

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