Zymosan activates protein kinase A via adenylyl cyclase VII to modulate innate immune responses during inflammation

Lily I. Jiang, Paul C. Sternweis, Jennifer E. Wang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Pathogens use a variety of strategies to evade host immune defenses. A powerful way to suppress immune function is to increase intracellular concentrations of cAMP in host immune cells, which dampens inflammatory responses and prevents microbial killing. We found that the yeast cell wall extract, zymosan, is capable of increasing intracellular cAMP and activates the protein kinase A pathway in bone marrow derived macrophage (BMDM) cells from mice. This response is dependent on adenylyl cyclase type VII (AC7) and heterotrimeric G proteins, primarily G12/13. Consequently, zymosan induced production of the inflammatory cytokine, TNFα, was much stronger in BMDMs from AC7 deficient mice compared to the response in wild type cells. In a model of zymosan induced peritonitis, mice deficient of AC7 in the myeloid lineage displayed prolonged inflammation. We propose that zymosan induced increases in cAMP and activation of PKA serve as a mechanism to dampen inflammatory responses in host cells, which consequently favors the survival of microbes. This would also help explain a well documented phenomenon, that the ability of zymosan to stimulate inflammatory cytokine responses via TLR2 appears to be weaker than other stimuli of TLR2.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalMolecular Immunology
Volume54
Issue number1
DOIs
StatePublished - May 1 2013

    Fingerprint

Keywords

  • Adenylyl cyclase
  • BRET
  • CAMP
  • G
  • PKA
  • Zymosan

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this