Inflammasome activation restricts Legionella pneumophila replication in primary microglial cells through flagellin detection.
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.
Bacterial Pathogenesis and Innate Immunity laboratory, Inserm U851 "Immunity, Infection and Vaccination," Claude Bernard Lyon I University, Lyon, France.
Yvan
Y
Jamilloux
Roberto
R
Pierini
Mathieu
M
Querenet
Carole
C
Juruj
Anne-Laure
AL
Fauchais
Marie-Odile
MO
Jauberteau
Sophie
S
Jarraud
Gérard
G
Lina
Jérôme
J
Etienne
Craig R
CR
Roy
Thomas
T
Henry
Nathalie
N
Davoust
Florence
F
Ader
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology; D002478:Cells, Cultured; D005408:Flagellin / Q000378:metabolism* / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism* / Q000502:physiology; D058847:Inflammasomes / Q000378:metabolism* / Q000502:physiology; D016952:Legionella pneumophila / Q000254:growth & development / Q000472:pathogenicity*; D007877:Legionnaires' Disease / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology*; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D006131:Growth Inhibitors; D058847:Inflammasomes; C512299:Ipaf protein, mouse; C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D005408:Flagellin