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

EMBO Reports
Kourosh GharunPhilipp Henneke

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.

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Citations

Feb 6, 2018·Annual Review of Immunology·Antonio J Pagán, Lalita Ramakrishnan
Jun 17, 2020·The Journal of Cell Biology·Helen Weavers, Paul Martin
Jun 7, 2018·Journal of Cell Science·Marie PereiraJacques Behmoaras
Aug 9, 2020·Journal of Leukocyte Biology·Anne Kathrin Lösslein, Philipp Henneke
Dec 22, 2020·Frontiers in Veterinary Science·Sophie PeterhansGiovanni Ghielmetti
Apr 3, 2021·Nature Communications·Anne Kathrin LössleinPhilipp Henneke
Jul 24, 2021·Cellular and Molecular Life Sciences : CMLS·Ophélie DufrançaisChristel Vérollet

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