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Updated: May 14, 2026
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
Inflammasome activation restricts Legionella pneumophila replication in primary microglial cells through flagellin
Yvan Jamilloux1, Roberto Pierini, Mathieu Querenet
1Bacterial Pathogenesis and Innate Immunity laboratory, Inserm U851 "Immunity, Infection and Vaccination," Claude Bernard Lyon I University, Lyon, France.
Abstract:
Microglial cells constitute the first line of defense of the central nervous system (CNS) against microbial invasion. Pathogens are detected thanks to an array of innate immune receptors termed pattern recognition receptors (PRRs). PRRs have been thoroughly characterized in bone marrow-derived macrophages, but the PRRs repertoire and functionality in microglial cells remain largely unknown. Microglial cells express various Toll-like Receptors and the Nod1/2 receptors. Recently, a novel innate immune signalling pathway, the inflammasome pathway has been uncovered. Inflammasome activation leads to caspase-1 activation, release of the proinflammatory cytokines, IL-1β and IL-18 and cell death in a process termed pyroptosis. One inflammasome receptor, NLRP3, has been characterized in microglial cells and associated with response to infections and in the initiation of neuro-degeneration in an Alzheimer's disease model. Legionella pneumophila (L.pneumophila) is a flagellated bacterium replicating within macrophages. In bone marrow-derived macrophages, L. pneumophila is detected in a flagellin-dependent manner by the Naip5-NLRC4 (Ipaf) inflammasome pathway. In this study, we decided to use L. pneumophila to investigate the presence and the functionality of this inflammasome in primary murine microglial cells. We show that microglial cells detect L. pneumophila infection in a flagellin-dependent manner leading to caspase-1-mediated bacterial growth restriction, infected cell death and secretion of the proinflammatory cytokines IL-1β and IL18. Overall, our data demonstrate that microglial cells have a functional Naip5-NLRC4 inflammasome likely to be important to monitor and clear CNS infections by flagellated bacteria.
Insights
Microglial cells, the CNS immune cells, possess a functional Naip5-NLRC4 inflammasome. This pathway detects flagellated bacteria like L. pneumophila, controlling infections and promoting cell death.
Area of Science:
- Neuroimmunology
- Innate Immunity
- Microbiology
Background:
- Microglial cells are the primary immune cells in the central nervous system (CNS).
- Pattern recognition receptors (PRRs) detect pathogens, but their repertoire in microglia is not fully understood.
- The inflammasome pathway, including NLRP3, is involved in neuroinflammation and neurodegeneration.
Purpose of the Study:
- To investigate the presence and function of the Naip5-NLRC4 inflammasome in primary murine microglial cells.
- To determine if microglia can detect flagellated bacteria via this inflammasome pathway.
Main Methods:
- Primary murine microglial cells were infected with Legionella pneumophila (L. pneumophila).
- Flagellin-dependent detection and caspase-1 activation were assessed.
- Bacterial growth, cytokine secretion (IL-1β, IL-18), and cell death were measured.
Main Results:
- Microglial cells detected L. pneumophila infection in a flagellin-dependent manner.
- Activation of the Naip5-NLRC4 inflammasome led to caspase-1-mediated bacterial growth restriction.
- Infected microglial cells underwent pyroptosis, releasing IL-1β and IL-18.
Conclusions:
- Primary microglial cells possess a functional Naip5-NLRC4 inflammasome.
- This inflammasome plays a crucial role in responding to flagellated bacterial infections in the CNS.
- The findings suggest a mechanism for monitoring and clearing CNS infections by flagellated bacteria.
