Abstract
ABSTRACTThe Dot/Icm type IV secretion system (T4SS) of Legionella pneumophila is essential for lysosomal evasion and permissiveness of macrophages for intracellular proliferation of the pathogen. In contrast, we show that polymorphonuclear cells (PMNs) respond to a functional Dot/Icm system through rapid restriction of L. pneumophila. Specifically, we show that the L. pneumophila T4SS-injected amylase (LamA) effector catalyzes rapid glycogen degradation in the PMNs cytosol, leading to cytosolic hyperglucose. Neutrophils respond through immunometabolic reprogramming that includes upregulated aerobic glycolysis. The PMNs become activated with spatial generation of intracellular reactive oxygen species within the Legionella-containing phagosome (LCP) and fusion of specific and azurophilic granules to the LCP, leading to rapid restriction of L. pneumophila. We conclude that in contrast to macrophages, PMNs respond to a functional Dot/Icm system, and specifically to the effect of the injected amylase effector, through rapid engagement of major microbicidal processes and rapid restriction of the pathogen.
Highlights
The Dot/Icm type IV secretion system (T4SS) of Legionella pneumophila is essential for lysosomal evasion and permissiveness of macrophages for intracellular proliferation of the pathogen
When phagocytosis of L. pneumophila by polymorphonuclear cells (PMNs) was blocked by cytochalasin D, translocation of L. pneumophila T4SS-injected amylase (LamA) was not detected by attached extracellular wild-type bacteria (Fig. 1A), demonstrating that LamA was only translocated into the PMNs’ cytosol upon phagocytosis of L. pneumophila
We examined if increased glycolysis in response to LamA-dependent cytosolic hyperglucose resulted in PMNs activation and rapid killing of L. pneumophila
Summary
The Dot/Icm type IV secretion system (T4SS) of Legionella pneumophila is essential for lysosomal evasion and permissiveness of macrophages for intracellular proliferation of the pathogen. We conclude that in contrast to macrophages, PMNs respond to a functional Dot/Icm system, and to the effect of the injected amylase effector, through rapid engagement of major microbicidal processes and rapid restriction of the pathogen. The Dot/Icm type IV translocation system of L. pneumophila, which functions as a molecular syringe, injects ;350 different protein effectors into the host cell cytosol to evade lysosomal fusion and overrides restriction of pathogen proliferation in both amoebae and alveolar macrophages [12,13,14,15,16,17,18,19]. PMNs account for 50 to 60% of peripheral blood leukocytes in humans and are an essential part of the innate immune defense against microbial infections
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
