Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells

Zachary C. Hartman, Esther P. Black, Andrea Amalfitano

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Adenovirus vectors are known to induce certain genes and impact innate response networks, but a broad understanding of this process and its mechanisms is currently lacking. For this reason, we chose to investigate and characterize Ad innate immunity using homogeneous, primary MEF cells replete with all the elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an array-based approach to maximally define transcriptome changes induced upon Ad vector infection, we discovered that Ad infection induces a potent gene and transcription factor network response. This response is characterized by significant changes in the expression of genes involved in focal adhesion, tight junction, and RNA regulation, in addition to TLR pathway and other innate sensing genes. Further investigation using human A549 cells knocked down for various TLR pathway adaptors, revealed significant impacts on the Ad initiation of NF-kB and interferon responses, thus confirming TLR involvement in Ad-mediated immunity across diverse species.

Original languageEnglish
Pages (from-to)357-372
Number of pages16
JournalVirology
Volume358
Issue number2
DOIs
StatePublished - Feb 20 2007

Bibliographical note

Funding Information:
We would like to thank Delila Serra and Jun-Ping Wei for technical support in virus preparation and EMSA technical expertise; Drs. Peter Haverty and Ulas Karaoz for logistical support and help with the ROVER and CARRIE analyses; as well Dr. Joseph Nevins and P. Yao at Duke University. AA and ZH were supported in part by a grant from the Children's Miracle Network (Durham, NC), AA was further supported by NIH grants (RO1DK-069884, P01 CA078673) and the Osteopathic Heritage Foundation. Appendix A

Keywords

  • Ad
  • Innate immune response
  • Microarray
  • Toll-like receptor

ASJC Scopus subject areas

  • Virology

Fingerprint

Dive into the research topics of 'Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells'. Together they form a unique fingerprint.

Cite this