title: Induction of rapid cell death by an environmental isolate of Legionella pneumophila in mouse macrophages.
abstract: Legionella pneumophila, the etiological agent for Legionnaires' disease, is ubiquitous in the aqueous environment, where it replicates as an intracellular parasite of free-living protozoa. Our understanding of L. pneumophila pathogenicity is obtained mostly from study of derivatives of several clinical isolates, which employ almost identical virulent determinants to exploit host functions. To determine whether environmental L. pneumophila isolates interact similarly with the model host systems, we analyzed intracellular replication of several recently isolated such strains and found that these strains cannot productively grow in bone marrow-derived macrophages of A/J mice, which are permissive for all examined laboratory strains. By focusing on one strain called LPE509, we found that its deficiency in intracellular replication in primary A/J macrophages is not caused by the lack of important pathogenic determinants because this strain replicates proficiently in two protozoan hosts and the human macrophage U937 cell. We also found that in the early phase of infection, the trafficking of this strain in A/J macrophages is similar to that of JR32, a derivative of strain Philadelphia 1. Furthermore, infection of these cells by LPE509 caused extensive cell death in a process that requires the Dot/Icm type IV secretion system. Finally, we showed that the cell death is caused neither by the activation of the NAIP5/NLRC4 inflammasome nor by the recently described caspase 11-dependent pathway. Our results revealed that some environmental L. pneumophila strains are unable to overcome the defense conferred by primary macrophages from mice known to be permissive for laboratory L. pneumophila strains. These results also suggest the existence of a host immune surveillance mechanism differing from those currently known in responding to L. pneumophila infection.
authors.affiliation: Department of Pulmonary Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tao
authors.forename: Wenhan
authors.initials: W
authors.lastname: Zhu
authors.forename: Bi-Jie
authors.initials: BJ
authors.lastname: Hu
authors.forename: Jie-Ming
authors.initials: JM
authors.lastname: Qu
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism; D007877:Legionnaires' Disease / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: D051017:Apoptosis Regulatory Proteins; D058847:Inflammasomes; D051616:Neuronal Apoptosis-Inhibitory Protein; D020169:Caspases