E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

Humoral immune responses during acute bacterial urinary tract infection in mice (#204)

Sophia Hawas 1 , Ashraful Haque 2 , Makrina Totsika 1
  1. Centre for Infection and Immunity Control, Queensland University of Technology, Brisbane, QLD, Australia
  2. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia

Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates in women1. With the rise of multi-drug resistant (MDR) bacteria, UTI treatment is becoming increasingly difficult, at great cost to healthcare systems2. Here we investigated whether protective adaptive immune responses occur in a mouse model of MDR UTI.

C57BL/6J wild-type or rag1-/-mice were transurethrally inoculated with an MDR UTI strain of Gram-negative uropathogenic Escherichia coli, depositing bacteria directly into the bladder3. Flow cytometry was used to characterise immune cell populations in bladder-draining lymph nodes of wild-type mice. Bladders and urine were also collected at various time-points to assess bacterial numbers.

In bladder-draining lymph nodes, germinal centre (GC) B cell responses had developed by 4 weeks post-infection, with immunoglobulin class switching towards IgG. GC B cell responses varied between individual infected wild-type mice. 30% of wild-type mice cleared bladder infection by 4 weeks, but we noted no clear correlation between the magnitude of GC B cell responses and bacterial load. At this timepoint, rag1-/-mice had significantly higher loads of bacteria in their bladders compared to wild-type mice, suggesting a role for adaptive immune responses in protecting against UTI.  In conclusion, our data suggests for the first time in a mouse model, that Gram-negative bacterial UTI induces humoral immune responses in local lymph nodes draining the bladder, and that these responses could potentially help clear infection.

  1. Geerlings, S. E. Clinical Presentations and Epidemiology of Urinary Tract Infections. Microbiol Spectr 4, doi:10.1128/microbiolspec.UTI-0002-2012 (2016).
  2. Foxman, B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon 49, 53-70, doi:10.1067/mda.2003.7 (2003).
  3. Hannan, T. J. & Hunstad, D. A. A Murine Model for Escherichia coli Urinary Tract Infection. Methods Mol Biol 1333, 159-175, doi:10.1007/978-1-4939-2854-5_14 (2016).