Naslov
Paradoxical Pro-inflammatory Responses by Human Macrophages to an Amoebae Host-Adapted Legionella Effector

Autori
Price, Christopher ; Jones, Snake ; Mihelcic, Mirna ; Santic, Marina ; Abu Kwaik, Yousef

Izvornik
Cell host & microbe (1931-3128) 27 (2020); 571-584

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Dot/Icm ; M1 ; amoebae ; amylase ; glycogen ; glycogenolysis ; legionella ; macrophage ; pro-inflammatory

Sažetak
Legionella pneumophila has co-evolved with amoebae, their natural hosts. Upon transmission to humans, the bacteria proliferate within alveolar macrophages causing pneumonia. Here, we show L. pneumophila injects the effector LamA, an amylase, into the cytosol of human macrophage (hMDMs) and amoebae to rapidly degrade glycogen to generate cytosolic hyper-glucose. In response, hMDMs shift their metabolism to aerobic glycolysis, which directly triggers an M1-like pro-inflammatory differentiation and nutritional innate immunity through enhanced tryptophan degradation. This leads to a modest restriction of bacterial proliferation in hMDMs. In contrast, LamA-mediated glycogenolysis in amoebae deprives the natural host from the main building blocks for synthesis of the cellulose-rich cyst wall, leading to subversion of amoeba encystation. This is non-permissive for bacterial proliferation. Therefore, LamA of L. pneumophila is an amoebae host-adapted effector that subverts encystation of the amoebae natural host, and the paradoxical hMDMs' pro-inflammatory response is likely an evolutionary accident.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA