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ExlA toxicity in vivo

Published on 19 February 2020
We first phenotypically analyzed ExlA-positive cohort collected worldwide revealing differential levels of expression of virulence factors and different motility patterns [10]. In the mouse, ExlA promotes bacterial growth in infected lungs and dissemination in several organs. It induces major lesions in lung alveoli, owing to its capacity to trigger necrosis of epithelial and endothelial cells, hence provoking hemorrhages by rupture of the alveolo-capillary barrier [11].
P. aeruginosa-induced hyperinflammation is known to be deleterious for the host. Inflammation is orchestrated by inflammasome activation within resident macrophages, leading to caspase-1-dependent IL-1β maturation and pyroptosis. IHMA87, the ExlA-positive strain that was particularly studied in the lab, was able of inflammasome activation in bone marrow-derived macrophages, leading to pyroptosis and IL-1β secretion [12].
To understand the role of inflammasome in IHMA87 infection in vivo, caspase-I-deficient and wild-type mice were infected using an acute pneumonia model. Infected mice survived better when they lacked caspase-1, indicating that the hyperinflammation induced by the presence of IHMA87 is detrimental for the animals. Some pro-inflammatory cytokines (IL-6, IL-17a and KC) are less produced and less neutrophils are recruited in caspase-I-deficient lungs.
Thus, as for T3SS-positive strains, IHMA87 triggers an excessive inflammasome-dependent inflammatory response that is deleterious for the host.


Macrophage damage induced by Pseudomonas aeruginosa (ExlA+) strain.

References
[10] Reboud et al (2016) Environmental microbiology 18(10):3425-3439.,
[11] Bouillot et al (2017) Scientific reports 7(1):2120.,
[12] Basso et al (2017) Environmental microbiology 19(10):4045-4064.