Mycobacterial para-Hydroxybenzoic Acid-Derivatives (pHBADs) and Related Structures Induce Macrophage Innate Memory

Mimmi Lundahl, Dylan M. Lynch, Danielle Barnes, Lauren McSweeney, Aoife Gorman, Filipa Lebre, Stephen V. Gordon, Ed C. Lavelle, Eoin M. Scanlan (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Macrophages are key immune cells for combatting Mycobacterium tuberculosis. However, M. tuberculosis possesses means to evade macrophage bactericidal responses by, for instance, secretion of the immunomodulatory para-hydroxybenzoic acid derivatives (pHBADs). While these molecules have been implicated in inhibiting macrophage responses in an acute context, little is known about their ability to reprogram macrophages via induction of long-term innate memory. Since innate memory has been highlighted as a promising strategy to augment bactericidal immune responses against M. tuberculosis, investigating corresponding immune evasion mechanisms is highly relevant. Our results reveal for the first time that pHBAD I and related molecules (unmethylated pHBAD I and the hexose l-rhamnose) reduce macrophage bactericidal mechanisms in both the short- A nd the long-term. Moreover, we demonstrate how methyl-p-anisate hinders bactericidal responses soon after exposure yet results in enhanced pro-inflammatory responses in the long-term. This work highlights new roles for these compounds in M. tuberculosis pathogenesis.

Original languageEnglish
Pages (from-to)2415-2421
Number of pages7
JournalACS Chemical Biology
Volume15
Issue number9
Early online date7 Aug 2020
DOIs
Publication statusPublished - 18 Sept 2020

Keywords

  • Bacteria
  • Circuits
  • Immunology
  • Infectious diseases
  • Peptides and proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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