Chronic prostate inflammation induced by E. coli infection induces tissue lesions associated to prostate cancer development.

SALAZAR, FLORENCIA C.; GODOY, GLORIA J.; OLIVERA, CAROLINA; RIVERO, VIRGINIA E.; MOTRICH, RUBEN D.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

Prostate cancer (CaP) is the second most frequent type of cancer in men. Prostate carcinogenesis is multifactorial and several environmental and genetic factors are involved. In this set, chronic inflammation was suggested as an important risk factor by several epidemiological studies. Herein, and using an animal model, we analyzed if chronic prostate inflammation caused by Escherichia coli infection may have a role in prostate carcinogenesis.Male C57BL/6 mice were transurethrally inoculated with 2x108 CFU of uropathogenic E. coli 1677 (infected) or saline (controls), euthanized at 5 days (dpi), 12 and 26 weeks (wpi) post infection, and the immune response, prostate infiltrating leukocytes and histopathology analyzed.Inoculated animals developed an ascending infection early after infection (5 dpi) that persisted along time (12 and 26 wpi). Infection induced inflammation that was characterized by significantly increased circulating IL17+ and IFNg+ T cells when compared with controls (p<0,05), either at early (5 dpi) or late times after inoculation (12 and 26 wpi). The peripheral immune response was accompanied by histological lesions in the prostate from infected mice. Several acute inflammation foci, mainly composed of Gr1+ cell infiltrates, hemorrhage, necrotic debris, abundant epithelial shedding and tissue disorganization were shown at 5 dpi. Later on, prominent chronic inflammation was evident by dense infiltrates in the stroma, mostly composed of CD3+ and CD11c+ cells (12 and 26 dpi). Strikingly, sites of intense inflammation were associated with shedding of epithelial cells, papillomatosis, and varying degrees of atypical hyperplasia and dysplastic changes mimicking high grade prostate intraepithelial neoplasia.Our results indicate that chronic bacterial infection of the prostate induces chronic inflammation associated in close proximity with tissue changes similar to neoplastic lesions, which could constitute a potential precursor of prostate adenocarcinoma.