Junior Research Fellow Institute of Infectious Disease and Molecular Medicine, University of Cape Town Cape Town, Western Cape, South Africa
Background Chlamydia trachomatis is a leading cause of poor reproductive health outcomes in women and may also increase HIV risk. Infections are often asymptomatic and undiagnosed in developing countries, where syndromic management is standard-of-care. Studies from South Africa estimate a prevalence of up to 40% in adolescent girls, which has undoubtedly increased due to disruption of health services during the pandemic. Chlamydia remains a major health concern, with vaccines urgently required. Although there is some evidence for partial protection after natural infection, this is poorly defined, highlighting the need to understand chlamydia immunity in the context of its natural history. Thus, we characterised chlamydia-specific CD4+ T cell responses in highly exposed young women, to understand the impact of multiple exposures.
Methods T cell responses were measured by multiparameter flow cytometry in HIV-uninfected young women (16-22 years old) with either confirmed chlamydia infection (NAAT+) or positive IgG ELISA (n=45). PBMCs were stimulated with a single peptide pool covering C. trachomatis major outer membrane protein and intracellular IFN-γ, IL-2 and TNF-α measured in CD3+CD4+ T cells. Non-parametric statistical tests were used for all data analysis.
Results Of the 45 women included in the study, 24/45 (53%) were experiencing a primary chlamydia infection (NAAT+/IgG-); 16/45 (36%) had a persistent/recurrent infection (NAAT+/IgG+); and 5/45 (11%) were NAAT-/IgG+, considered evidence of previous/recovered infection. All recovered women had detectable chlamydia-specific CD4+ T cells producing any cytokine, compared to ~80% of women with active infection (NAAT+/IgG+ or NAAT+/IgG-). Notably, CD4+ IFN-γ+ T cells were found in all five recovered women, but in only 50% and 33% of women with persistent and primary infections, respectively. Consequently, recovered women had a significantly higher frequency of chlamydia-specific CD4+T cells producing IFN-γ than those with primary infections (p=0.007). We also found a weak positive correlation between chlamydia-specific CD4+ IFN-γ responses and the relative concentrations of chlamydia-specific IgG (r=0.31, p=0.036).
Conclusion We report an important potential association between chlamydia-specific Th1/IFN-γ responses and relative exposure in young women, which may reflect immune cell migration dynamics during active infection. These findings may have significant implications for mucosal vaccine strategies and evaluation and should be explored further.
