Despite the high prevalence of chlamydia in men, there is very little known about the host response to chlamydial genital infection in the males; in particular the nature of the local response in the urethra is virtually unknown in contrast to the extensively studied disease pathogenesis and protective immune response in females. However, it has been shown that the male guinea pig model can be infected by an intra-urethral inoculation with chlamydiae. Moreover, the humoral response was required for the control of chlamydial infection in male urogenital tracts, and male guinea pigs developed high resistance to reinfection after a primary infection. Therefore, this study aimed to further characterize the pathologic and local immunologic response to urethral infection of the male guinea pig with Chlamydia caviae during both a primary infection and following a challenge infection.
The histopathologic response in infected male urethrae was similar to the female, featuring an initial acute inflammatory response followed by a chronic inflammatory response and plasma cell infiltration. Production of chlamydia-specific IgG and IgA antibodies in local urethral secretions developed following infection. A strong proliferative T lymphocyte response was elicited in iliac lymph nodes as early as day 7 following a primary infection, in contrast to that in spleens. CD4 and CD8 T cells, as well as B cells, were observed in the local site by flow cytometry with a slightly more increase of CD8+ cells than that of CD4+ cells. The T cell response was clearly a Th1-like response as judged by increased levels of IFN-γ, IL-12p40, and IL-2. Proinflammatory cytokines and chemokines, IL-8, IL-1β, TNF-α, CCL2 (MCP-1), and CCL5 (RANTES) were elicited in the urethral tissues following primary infection.
Both chlamydial specific IgG and IgA increased in a typical anamnestic response in urethral secretions following a challenge infection. Interestingly, the dominant anamnestic response was solely in the B cell compartment with only a minimal number of T cells after reinfection. In general, the chemokine and cytokine response following challenge was markedly reduced. Moreover, the local cytokine and chemokine response in male urethras was also determined compared to that in female cervixes after a genital chlamydial reinfection. Preliminary results suggested expression profiles of cytokines such as IL-2, GM-CSF and MCP-1 were different in genital tissues after reinfection between male and female guinea pigs. Taken together, the host response in the male urethra with respect to both the inflammatory response and both the humoral and cell-mediated immune responses was characterized to better understand the immunopathogenesis of chlamydial genital infection in males.
|Advisor:||Rank, Roger G.|
|School:||University of Arkansas for Medical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 71/01, Dissertation Abstracts International|
|Keywords:||Chlamydia, Host response, Urethral infection|
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