Frontline Science: Antibiotic treatment routes Mycobacterium avium to phagolysosomes without triggering proinflammatory cytokine production in human Mϕs. Issue 1 (12th June 2020)

• Record Type: Journal Article
• Authors: Åsberg, Signe Elisabeth; Mediaas, Sindre Dahl; Marstad, Anne; Ryan, Liv; Louet, Claire; Sporsheim, Bjørnar; Beckwith, Kai Sandvold; Underhill, David Michael; Gidon, Alexandre; Flo, Trude Helen
• Is Part Of: Journal of leukocyte biology. Volume 109:Issue 1(2021)
• Page Start: 23
• Page End: 33
• Publication Date: 2020-06-12
• Subjects: inflammation, host-pathogen -- infection biology, intracellular trafficking, compartmentalized signaling, human primary Mϕs; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.4HI0420-306R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Mycobacterium avium (Mav) causes chronic infections in immunocompromised patients that require long-term antibiotic treatment. We have previously shown that Mav takes residence in host Mϕs and establishes a compartment (MavC) in which it is hidden from host defenses. Failure to establish the MavC traps Mav in Lamp1 + phagolysosomes where growth is prevented, and inflammatory signaling activated through TLRs 7/8. To elucidate how antibiotic treatment affects mycobacterial trafficking and host defenses, we infected human primary Mϕs with Mav for 4 days prior to treatment with a macrolide, aminoglycoside, and ethambutol. We show that Mav is killed and the MavC fuses with Lamp1 + lysosomes following antibiotic treatment. However, this does not result in nuclear translocation of NF-κB or production of inflammatory cytokines, suggesting different Lamp1 + lysosomal compartments can form that differ in their innate signaling capabilities. Thus, we show that upon antibiotic treatment of a chronic infection, Mav is quietly disposed of by Mϕs. Graphical Abstract: M. avium is quietly disposed of by macrophages upon antibiotic treatment