NLRP3 inflammasome is dispensable in methicillin resistantStaphylococcus aureusurinary tract infection

Abstract

AbstractNLRP3 inflammasome is a cytoplasmic complex that senses molecular patterns from pathogens or damaged cells to trigger an innate immune defense response marked by the production of proinflammatory cytokines IL-1β and IL-18 and an inflammatory death called pyroptosis. The NLRP3 inflammasome is activated in the urinary tract by a variety of infectious and non-infectious insults. In this study, we investigated the role of NLRP3 inflammasome by inducing methicillin resistantStaphylococcus aureus(MRSA) ascending UTI in WT andNlrp3-/-mice. At 24 and 72 hpi, compared to the WT, the MRSA-infectedNlrp3-/-showed ∼100-fold lower median CFUs, although this reduction was not statistically significant. The ablation of NLRP3 did not affect MRSA-induced urinary immune defenses as indicated by the similar levels of pro-inflammatory cytokines and chemokines and the similar numbers of granulocytes in the bladder and the kidneys of WT andNlrp3-/-mice at 24 h after MRSA infection. However, MRSA-infectedNlrp3-/-bladders, but not kidneys, showed significantly higher monocyte infiltration. The histopathological analysis of bladder and kidney sections showed similar inflammation in MRSA-infectedNlrp3-/-and WT mice. Overall, these results suggest that MRSA-induced urinary NLRP3 activity is dispensable to the host.ImportanceIndwelling urinary catheter usage increased susceptibility to methicillin-resistantStaphylococcus aureus(MRSA) urinary tract infections (UTI) which can be difficult to treat and can result in potentially fatal complications such as bacteremia, urosepsis, and shock. In this work, we examined the role of NLRP3 inflammasome in MRSA uropathogenesis. In comparison to the WT, mice deficient in NLRP3 activity showed similar MRSA burden and similar inflammation in the bladder and kidney tissues at 24 h after the experimental induction of ascending UTI. These results suggest that NLRP3 inflammasome is not involved in shaping urinary immune defenses during acute MRSA-UTI.