Frontline Science: Antibiotic treatment routes Mycobacterium avium to phagolysosomes without triggering proinflammatory cytokine production in human Mϕs.

Journal of Leukocyte Biology
Signe Elisabeth ÅsbergTrude Helen Flo

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.

References

Feb 6, 2007·American Journal of Respiratory and Critical Care Medicine·David E GriffithUNKNOWN Infectious Disease Society of America
May 12, 2009·Nature Immunology·Giuseppe MancusoConcetta Beninati
Mar 23, 2010·Cell·Osamu Takeuchi, Shizuo Akira
Jan 29, 2011·Clinical & Developmental Immunology·Hiroyuki SaigaKiyoshi Takeda
Mar 25, 2011·Mucosal Immunology·A M CooperA Sher
Jul 12, 2011·Cellular Microbiology·Ka-Wing Wong, William R Jacobs
Aug 2, 2011·The Journal of Clinical Investigation·Maurizio RennaR Andres Floto
Apr 25, 2012·Cellular Microbiology·Diane HoubenPeter J Peters
Jul 6, 2012·Clinical Microbiology Reviews·Barbara A Brown-ElliottRichard J Wallace
Sep 5, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karin PelkaEicke Latz
Oct 10, 2014·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·S K BrodeT K Marras
Oct 11, 2014·Cold Spring Harbor Perspectives in Biology·Surya PandeyShizuo Akira
Jan 13, 2015·Annual Review of Immunology·Sky W BrubakerJonathan C Kagan
Jun 19, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bjarte BergstrømJørgen Stenvik
Jul 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jane Atesoh AwuhTrude Helen Flo
Apr 12, 2016·Tuberculosis and Respiratory Diseases·Yon Ju RyuCharles L Daley
Sep 1, 2016·Journal of Leukocyte Biology·Andrea J WolfDavid M Underhill
Oct 30, 2016·Cellular Microbiology·Jin Kyung KimEun-Kyeong Jo
Nov 21, 2016·Cellular and Molecular Life Sciences : CMLS·Jane Atesoh Awuh, Trude Helen Flo
Apr 22, 2017·Microbiology Spectrum·Charles L Daley
Apr 28, 2017·The European Respiratory Journal·D Rebecca PrevotsGiovanni Battista Migliori
Feb 17, 2018·International Immunology·Kensuke MiyakeYusuke Murakami
Apr 6, 2018·Nature Reviews. Molecular Cell Biology·Ivan Dikic, Zvulun Elazar
Jan 11, 2019·Cell Host & Microbe·Mihai G NeteaJoachim L Schultze
Feb 4, 2019·Tuberculosis·Caroline BusattoPedro Eduardo Almeida da Silva
Feb 23, 2019·Journal of Cell Science·Bradlee L Heckmann, Douglas R Green
Jun 20, 2019·Nature Immunology·Gioacchino Natoli, Renato Ostuni
Jun 21, 2019·Journal of Leukocyte Biology·Kensuke MiyakeYusuke Murakami
Oct 12, 2019·F1000Research·David Horne, Shawn Skerrett

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Citations

Aug 9, 2020·Journal of Leukocyte Biology·Anne Kathrin Lösslein, Philipp Henneke

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