TY - JOUR
T1 - Mycobacteria exploit nitric oxide-induced transformation of macrophages into permissive giant cells
AU - Gharun, Kourosh
AU - Senges, Julia
AU - Seidl, Maximilian
AU - Lösslein, Anne
AU - Kolter, Julia
AU - Lohrmann, Florens
AU - Fliegauf, Manfred
AU - Elgizouli, Magdeldin
AU - Vavra, Martina
AU - Schachtrup, Kristina
AU - Illert, Anna L.
AU - Gilleron, Martine
AU - Kirschning, Carsten J.
AU - Triantafyllopoulou, Antigoni
AU - Henneke, Philipp
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/12
Y1 - 2017/12
N2 - Immunity to mycobacteria involves the formation of granulomas, characterized by a unique macrophage (MΦ) species, so-called multinucleated giant cells (MGC). It remains unresolved whether MGC are beneficial to the host, that is, by prevention of bacterial spread, or whether they promote mycobacterial persistence. Here, we show that the prototypical antimycobacterial molecule nitric oxide (NO), which is produced by MGC in excessive amounts, is a double-edged sword. Next to its antibacterial capacity, NO propagates the transformation of MΦ into MGC, which are relatively permissive for mycobacterial persistence. The mechanism underlying MGC formation involves NO-induced DNA damage and impairment of p53 function. Moreover, MGC have an unsurpassed potential to engulf mycobacteria-infected apoptotic cells, which adds a further burden to their antimycobacterial capacity. Accordingly, mycobacteria take paradoxical advantage of antimicrobial cellular efforts by driving effector MΦ into a permissive MGC state.
AB - Immunity to mycobacteria involves the formation of granulomas, characterized by a unique macrophage (MΦ) species, so-called multinucleated giant cells (MGC). It remains unresolved whether MGC are beneficial to the host, that is, by prevention of bacterial spread, or whether they promote mycobacterial persistence. Here, we show that the prototypical antimycobacterial molecule nitric oxide (NO), which is produced by MGC in excessive amounts, is a double-edged sword. Next to its antibacterial capacity, NO propagates the transformation of MΦ into MGC, which are relatively permissive for mycobacterial persistence. The mechanism underlying MGC formation involves NO-induced DNA damage and impairment of p53 function. Moreover, MGC have an unsurpassed potential to engulf mycobacteria-infected apoptotic cells, which adds a further burden to their antimycobacterial capacity. Accordingly, mycobacteria take paradoxical advantage of antimicrobial cellular efforts by driving effector MΦ into a permissive MGC state.
KW - macrophages
KW - multinucleated giant cells
KW - mycobacteria
KW - nitric oxide
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=85032788114&partnerID=8YFLogxK
U2 - 10.15252/embr.201744121
DO - 10.15252/embr.201744121
M3 - Article
C2 - 29097394
AN - SCOPUS:85032788114
SN - 1469-221X
VL - 18
SP - 2144
EP - 2159
JO - EMBO Reports
JF - EMBO Reports
IS - 12
ER -