Premium
Frontline Science: Antibiotic treatment routes Mycobacterium avium to phagolysosomes without triggering proinflammatory cytokine production in human Mϕs
Author(s) -
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
Publication year - 2021
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.4hi0420-306r
Subject(s) - biology , microbiology and biotechnology , proinflammatory cytokine , antibiotics , immunology , cytokine , inflammation
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.