Inflammasome activation by Pseudomonas aeruginosa's ExlA pore-forming toxin is detrimental for the host.
During acute Pseudomonas aeruginosa infection, the inflammatory response is essential for bacterial clearance. Neutrophil recruitment can be initiated following the assembly of an inflammasome within sentinel macrophages, leading to activation of caspase-1, which in turn triggers macrophage pyroptosis and IL-1β/IL-18 maturation. Inflammasome formation can be induced by a number of bacterial determinants, including Type III secretion systems (T3SSs) or pore-forming toxins, or, alternatively, by lipopolysaccharide (LPS) via caspase-11 activation. Surprisingly, previous studies indicated that a T3SS-induced inflammasome increased pathogenicity in mouse models of P. aeruginosa infection. Here, we investigated the immune reaction of mice infected with a T3SS-negative P. aeruginosa strain (IHMA879472). Virulence of this strain relies on ExlA, a secreted pore-forming toxin. IHMA879472 promoted massive neutrophil infiltration in infected lungs, owing to efficient priming of toll-like receptors, and thus enhanced the expression of inflammatory proteins including pro-IL-1β and TNF-α. However, mature-IL-1β and IL-18 were undetectable in wild-type mice, suggesting that ExlA failed to effectively activate caspase-1. Nevertheless, caspase-1/11 deficiency improved survival following infection with IHMA879472, as previously described for T3SS+ bacteria. We conclude that the detrimental effect associated with the ExlA-induced inflammasome is probably not due to hyperinflammation, rather it stems from another inflammasome-dependent process.
['Bouillot|Stéphanie|S|', 'Pont|Stéphane|S|', 'Gallet|Benoit|B|', 'Moriscot|Christine|C|', 'Deruelle|Vincent|V|', 'Attrée|Ina|I|', 'Huber|Philippe|P|0000-0002-4153-7694']
D000818:Animals D016207:Cytokines D058847:Inflammasomes D007249:Inflammation D053582:Interleukin-1alpha D053583:Interleukin-1beta D007956:Leukocidins D008168:Lung D008264:Macrophages D051379:Mice D020556:Neutrophil Infiltration D010446:Peptide Fragments D011552:Pseudomonas Infections D011550:Pseudomonas aeruginosa D017472:Receptors, Interleukin-1 D000069296:Type III Secretion Systems D014774:Virulence
toxins virulence microbial-cell interaction pseudomonads