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Abstract: SA-PO616

NOD2 Activates Intercalated Cell Immune Defense During Uropathogenic Escherichia coli Infection

Session Information

  • Pediatric Nephrology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology


  • Linn, Sarah C., Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
  • Schwartz, Laura, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
  • Spencer, John David, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Urinary tract infections (UTIs), including pyelonephritis, are frequent infections in women and children often caused by uropathogenic Escherichia coli (UPEC). Intercalated cells (ICs), located within the collecting duct, prevent and combat UTIs by recruiting immune cells and secreting antimicrobial peptides (AMPs) into the urine. Mechanisms of UPEC pyelonephritis pathogenesis and the IC immune response are unclear. Here, we challenged ICs in vitro with UPEC or bacterial membrane constituents to identify their innate immune responses.


Rabbit ICs (Clone C cells) were challenged with UPEC or the UPEC cell membrane components lipopolysaccharide (LPS), muramyl dipeptide (MDP) and γ-D-Glu-mDAP (iE-DAP). Following infection, cell lysates were obtained and an antimicrobial response PCR array or qRT-PCR were used to determine immune gene activation. Immunoblotting was performed to confirm innate immune pathway activation. Bacterial attachment and invasion assays assessed if exposure to cell membrane components prior to infection impacted IC susceptibility to UPEC.


UPEC activated Toll-like receptor (TLR), NFkB, and Nucleotide Binding Oligomerization Domain Containing (NOD)-like receptor (NLR) signaling pathways in ICs, as determined by the antimicrobial response arrays, STRING, and Ingenuity Pathway Analysis. Immunoblotting confirmed activation of both NFkB and MAPK signaling pathways. LPS and the NOD2 agonist, MDP, stimulated NF-kB and MAPK signaling and induced AMP expression, including Lcn2 (NGAL), Ribonuclease 4, and Ribonuclease 8. The NOD1 agonist, iE-DAP did not affect AMP expression. Incubation of ICs with LPS and MDP one hour prior to infection protected ICs against UPEC attachment and invasion.


In response to UPEC, ICs activate NOD2, TLR4, and the downstream NFkB and MAPK signaling pathways. Stimulation with LPS and MDP activates IC innate immune pathways and increases AMP expression to protect ICs from UPEC. Together, these data indicate NOD2 and downstream NFkB and MAPK signaling may have a role in IC innate immune defenses against UTI.


  • NIDDK Support