PMID- 27936166 OWN - NLM STAT- MEDLINE DCOM- 20170710 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 12 DP - 2016 TI - Increased Age, but Not Parity Predisposes to Higher Bacteriuria Burdens Due to Streptococcus Urinary Tract Infection and Influences Bladder Cytokine Responses, Which Develop Independent of Tissue Bacterial Loads. PG - e0167732 LID - 10.1371/journal.pone.0167732 [doi] LID - e0167732 AB - Streptococcus agalactiae causes urinary tract infection (UTI) in pregnant adults, non-pregnant adults, immune-compromised individuals and the elderly. The pathogenesis of S. agalactiae UTI in distinct patient populations is poorly understood. In this study, we used murine models of UTI incorporating young mice, aged and dam mice to show that uropathogenic S. agalactiae causes bacteriuria at significantly higher levels in aged mice compared to young mice and this occurs coincident with equivalent levels of bladder tissue colonisation at 24 h post-infection (p.i.). In addition, aged mice exhibited significantly higher bacteriuria burdens at 48 h compared to young mice, confirming a divergent pattern of bacterial colonization in the urinary tract of aged and young mice. Multiparous mice, in contrast, exhibited significantly lower urinary titres of S. agalactiae compared to age-matched nulliparous mice suggesting that parity enhances the ability of the host to control S. agalactiae bacteriuria. Additionally, we show that both age and parity alter the expression levels of several key regulatory and pro-inflammatory cytokines, which are known to be important the immune response to UTI, including Interleukin (IL)-1beta, IL-12(p40), and Monocyte Chemoattractant Protein-1 (MCP-1). Finally, we demonstrate that other cytokines, including IL-17 are induced significantly in the S. agalactiae-infected bladder regardless of age and parity status. Collectively, these findings show that the host environment plays an important role in influencing the severity of S. agalactiae UTI; infection dynamics, particularly in the context of bacteriuria, depend on age and parity, which also affect the nature of innate immune responses to infection. FAU - Sullivan, Matthew J AU - Sullivan MJ AD - School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. FAU - Carey, Alison J AU - Carey AJ AD - School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. FAU - Leclercq, Sophie Y AU - Leclercq SY AD - School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. AD - Research and Development Center, Ezequiel Dias Foundation (Funed), Belo Horizonte, MG, Brazil. FAU - Tan, Chee K AU - Tan CK AD - School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. FAU - Ulett, Glen C AU - Ulett GC AUID- ORCID: 0000-0002-9638-8091 AD - School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. LA - eng PT - Journal Article DEP - 20161209 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Cytokines) SB - IM MH - Age Factors MH - Animals MH - Bacterial Load MH - Bacteriuria/*epidemiology/immunology/microbiology/pathology MH - Cytokines/analysis/immunology MH - Female MH - Humans MH - Mice MH - Mice, Inbred C57BL MH - *Parity MH - Pregnancy MH - Streptococcal Infections/*epidemiology/immunology/microbiology/pathology MH - Streptococcus agalactiae/immunology/*isolation & purification MH - Urinary Bladder/immunology/*microbiology/pathology MH - Urinary Tract Infections/*epidemiology/immunology/microbiology/pathology PMC - PMC5147962 COIS- The authors have declared that no competing interests exist. EDAT- 2016/12/10 06:00 MHDA- 2017/07/14 06:00 PMCR- 2016/12/09 CRDT- 2016/12/10 06:00 PHST- 2016/06/16 00:00 [received] PHST- 2016/11/18 00:00 [accepted] PHST- 2016/12/10 06:00 [entrez] PHST- 2016/12/10 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2016/12/09 00:00 [pmc-release] AID - PONE-D-16-24137 [pii] AID - 10.1371/journal.pone.0167732 [doi] PST - epublish SO - PLoS One. 2016 Dec 9;11(12):e0167732. doi: 10.1371/journal.pone.0167732. eCollection 2016.