Infectious
epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with
epididymitis is Escherichia coli. In our previous study, we showed that semen quality is compromised in men following
epididymitis associated with specific E. coli pathovars. Thus, our aim was to investigate possible differences in immune responses elicited during
epididymitis following
infection with the uropathogenic E. coli (UPEC) strain CFT073 and the nonpathogenic enteric E. coli (NPEC) strain 470. Employing an in vivo experimental
epididymitis model, C57BL/6 mice were infected with UPEC CFT073, NPEC 470, or
phosphate-buffered saline (PBS) as a
sham control for up to 7 days. After
infection with NPEC 470, the expression of proinflammatory
cytokines interleukin-1 (IL-1),
IL-6, and
tumor necrosis factor alpha in the epididymis was significantly increased. Conversely, UPEC CFT073-challenged mice displayed inflammatory gene expression at levels comparable to
sham PBS-treated animals. Moreover, by day 7 only NPEC-infected animals showed activation of adaptive immunity evident by a substantial influx of CD3+ and F4/80+ cells in the epididymal interstitium. This correlated with enhanced production of Th1-associated
cytokines IL-2 and
gamma interferon (IFN-γ). Furthermore, splenocytes isolated from UPEC-infected mice exhibited diminished T-cell responses with significantly reduced secretion of
IL-2 and IFN-γ in contrast to NPEC-infected animals. Overall, these findings provide new insights into understanding pathogen-specific modulation of host immunity during acute phases of
epididymitis, which may influence severity of disease and clinical outcomes.