Mycobacteria exploit nitric oxide-induced transformation of macrophages into permissive giant cells

Kourosh Gharun, Julia Senges, Maximilian Seidl, Anne Lösslein, Julia Kolter, Florens Lohrmann, Manfred Fliegauf, Magdeldin Elgizouli, Martina Vavra, Kristina Schachtrup, Anna L. Illert, Martine Gilleron, Carsten J. Kirschning, Antigoni Triantafyllopoulou, Philipp Henneke

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2144-2159
Number of pages16
JournalEMBO Reports
Volume18
Issue number12
DOIs
StatePublished - Dec 2017
Externally publishedYes

Keywords

  • macrophages
  • multinucleated giant cells
  • mycobacteria
  • nitric oxide
  • p53

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