Mouse macrophages are permissive to motile Legionella species that fail to trigger pyroptosis.
Legionella pneumophila, a motile opportunistic pathogen of humans, is restricted from replicating in the lungs of C57BL/6 mice. Resistance of mouse macrophages to L. pneumophila depends on recognition of cytosolic flagellin. Once detected by the NOD-like receptors Naip5 and Ipaf (Nlrc4), flagellin triggers pyroptosis, a proinflammatory cell death. In contrast, motile strains of L. parisiensis and L. tucsonensis replicate profusely within C57BL/6 macrophages, similar to flagellin-deficient L. pneumophila. To gain insight into how motile species escape innate defense mechanisms of mice, we compared their impacts on macrophages. L. parisiensis and L. tucsonensis do not induce proinflammatory cell death, as measured by lactate dehydrogenase (LDH) release and interleukin-1beta (IL-1beta) secretion. However, flagellin isolated from L. parisiensis and L. tucsonensis triggers cell death and IL-1beta secretion when transfected into the cytosol of macrophages. Neither strain displays three characteristics of the canonical L. pneumophila Dot/Icm type IV secretion system: sodium sensitivity, LAMP-1 evasion, and pore formation. Therefore, we postulate that when L. parisiensis and L. tucsonensis invade a mouse macrophage, flagellin is confined to the phagosome, protecting the bacteria from recognition by the cytosolic surveillance system and allowing Legionella to replicate. Despite their superior capacity to multiply in mouse macrophages, L. parisiensis and L. tucsonensis have been associated with only two cases of disease, both in renal transplant patients. These results point to the complexity of disease, a product of the pathogenic potential of the microbe, as defined in the laboratory, and the capacity of the host to mount a measured defense.
Whitfield
Natalie N
NN
Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Byrne
Brenda G
BG
Swanson
Michele S
MS
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D005408:Flagellin / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D007875:Legionella / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL
D005408:Flagellin