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Mycobacteria exploit nitric oxide‐induced transformation of macrophages into permissive giant cells
Author(s) -
Gharun Kourosh,
Senges Julia,
Seidl Maximilian,
Lösslein Anne,
Kolter Julia,
Lohrmann Florens,
Fliegauf Manfred,
Elgizouli Magdeldin,
Vavra Martina,
Schachtrup Kristina,
Illert Anna L,
Gilleron Martine,
Kirschning Carsten J,
Triantafyllopoulou Antigoni,
Henneke Philipp
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744121
Subject(s) - nitric oxide , permissive , transformation (genetics) , microbiology and biotechnology , chemistry , macrophage , biology , biochemistry , virology , in vitro , gene , organic chemistry
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.