TY - JOUR
T1 - Differential profiles of immune mediators and in vitro HIV infectivity between endocervical and vaginal secretions from women with Chlamydia trachomatis infection
T2 - A pilot study
AU - Sperling, Rhoda
AU - Kraus, Thomas A.
AU - Ding, Jian
AU - Veretennikova, Alina
AU - Lorde-Rollins, Elizabeth
AU - Singh, Tricia
AU - Lo, Yungtai
AU - Quayle, Alison J.
AU - Chang, Theresa L.
N1 - Funding Information:
This work was supported by NIH grant AI081559 to T.L.C. We thank Lyndsey Buckner for a critical reading of the manuscript.
PY - 2013/9
Y1 - 2013/9
N2 - Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection.
AB - Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection.
KW - Chlamydia trachomatis
KW - HIV infectivity in vitro.
KW - HIV transmission
KW - Immune mediators
KW - Lower genital tract
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U2 - 10.1016/j.jri.2013.07.003
DO - 10.1016/j.jri.2013.07.003
M3 - Article
C2 - 23993451
AN - SCOPUS:84883558451
SN - 0165-0378
VL - 99
SP - 80
EP - 87
JO - Journal of Reproductive Immunology
JF - Journal of Reproductive Immunology
IS - 1-2
ER -