Mycobacterial para-Hydroxybenzoic Acid-Derivatives (pHBADs) and Related Structures Induce Macrophage Innate Memory.
ACS Chem Biol
; 15(9): 2415-2421, 2020 09 18.
Article
de En
| MEDLINE
| ID: mdl-32786261
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- and 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Parabènes
/
Immunité innée
/
Facteurs immunologiques
/
Activation des macrophages
/
Macrophages
Limites:
Animals
Langue:
En
Journal:
ACS Chem Biol
Année:
2020
Type de document:
Article
Pays d'affiliation:
Irlande