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

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

Buenos Aires

Congreso; Reunión conjunta de Sociedades de biociencias.; 2017

Sociedad Argentina de Inmunologia,Sociedad Argentina de Investigación Clinica, Sociedad Argentina de Farmacología Experimental,Sociedad Argentina de Biologia, Sociedad Argentina de Andrología , entre otras

Prostate cancer (CaP) is the second most frequent type of cancerin men. Prostate carcinogenesis is multifactorial and severalenvironmental and genetic factors are involved. In this set, chronicinflammation was suggested as an important risk factor by severalepidemiological studies. Herein, and using an animal model, weanalyzed if chronic prostate inflammation caused by Escherichia coliinfection may have a role in prostate carcinogenesis.Male C57BL/6 mice were transurethrally inoculated with 2x108CFU 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 histopathologyanalyzed.Inoculated animals developed an ascending infection early afterinfection (5 dpi) that persisted along time (12 and 26 wpi). Infectioninduced inflammation that was characterized by significantlyincreased circulating IL17+ and IFNg+ T cells when compared withcontrols (p<0,05), either at early (5 dpi) or late times after inoculation(12 and 26 wpi). The peripheral immune response was accompaniedby histological lesions in the prostate from infected mice.Several acute inflammation foci, mainly composed of Gr1+ cell infiltrates,hemorrhage, necrotic debris, abundant epithelial sheddingand tissue disorganization were shown at 5 dpi. Later on, prominentchronic 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 sheddingof epithelial cells, papillomatosis, and varying degrees of atypicalhyperplasia and dysplastic changes mimicking high grade prostateintraepithelial neoplasia.Our results indicate that chronic bacterial infection of the prostateinduces chronic inflammation associated in close proximity with tissuechanges similar to neoplastic lesions, which could constitute apotential precursor of prostate adenocarcinoma.