Jaumdally, S. Z. | Search bioRxiv

bioRxiv2025

Circulating Chlamydia trachomatis-specific T Cell Immunity Reflects Widespread Exposure in South African Adolescents and Young Women

Chlamydia trachomatis remains the most prevalent bacterial sexually transmitted infection worldwide, with adolescent girls and young women (AGYW) disproportionately affected. Despite this, vaccine development is hindered by our limited understanding of protective immunity, particularly in the context of recurrent infections and immune-mediated pathology. Here, we characterised mucosal inflammation and systemic immune responses to C. trachomatis in South African AGYW (n=145), stratified by exposure history based on nucleic acid amplification testing (NAAT) and anti-C. trachomatis IgG levels. Cervicovaginal cytokines were quantified from menstrual cup secretions, and cervical and peripheral blood T cell activation assessed by flow cytometry. CD4+ T cell responses to recombinant MOMP were measured in a subset of 46 women who were NAAT-positive and/or seropositive. Untreated or recurrent C. trachomatis infection (NAAT+/IgG+) was associated with increased cervical T cell activation. All women with untreated or recurrent infections had detectable circulating C. trachomatis-specific CD4+ T cells in blood; however, response magnitude was 2.4-fold lower than in women with cleared or primary infections. Women with cleared infection had the highest proportions of C. trachomatis-specific multifunctional CD4+ T cells, while those with untreated or recurrent infections had almost none. Notably, systemic C. trachomatis-specific Th1 responses were inversely correlated with genital tract concentrations of inflammatory cytokines including IL-1{beta}, TNF, and IL-17. These findings demonstrate that both the magnitude and quality of the systemic CD4+ T cell responses are critical components of protective immunity to C. trachomatis, and may limit mucosal immunopathology, which has important implications for vaccine strategies and evaluation in high-risk populations.

immunology↗

bioRxiv2019

crAssphage abundance and genomic selective pressure correlate with altered bacterial abundance in the fecal microbiota of South African mother-infant dyads

crAssphages are a class of bacteriophages that are highly abundant in the human gastrointestinal tract. Accordingly, crAssphage genomes have been identified in most human fecal viral metagenome studies. However, we currently have an incomplete understanding of factors impacting the transmission frequencies of these phages between mothers and infants, and the evolutionary pressures associated with such transmissions. Here, we use metagenome sequencing of stool-associated virus-like particles to identify the prevalence of crAssphage across ten South African mother-infant dyads that are discordant for HIV infection. We report the identification of a complete 97kb crAssphage genome, parts of which are detected at variable levels across each mother-infant dyad. We observed average nucleotide sequence identities of >99% for crAssphages from related mother-infant pairs but [~]97% identities between crAssphages from unrelated mothers and infants: a finding strongly suggestive of vertical mother to infant transmission. We further analyzed patterns of nucleotide diversity across the crAssphage sequences described here, identifying particularly elevated positive selection in RNA polymerase and phage tail protein encoding genes, which we validated against a crAssphage genome from previous studies. Using 16S rRNA gene sequencing, we found that the relative abundances of Bacteroides thetaiotaomicron and Parabacteroides merdae (Order: Bacteroidales) were differentially correlated with crAssphage abundance. Together, our results reveal that crAssphages may be vertically transmitted from mothers to their infants and that hotspots of selection within crAssphage RNA polymerase and phage tail protein encoding genes are potentially mediated by interactions between crAssphages and their bacterial partners.\n\nImportancecrAssphages are an ubiquitous member of the human gut microbiome and modulate interactions with key bacterial associates within the order Bacteroidales. However, the role of this interaction in the genomic evolution of crAssphage remains unclear. Across a longitudinally sampled cohort of ten South African mother-infant dyads, we use metagenome sequencing of the fecal virome and 16S rRNA gene sequencing of the fecal bacterial microbiota to elucidate the ecological and evolutionary dynamics of these interactions. Here, we demonstrate elevated levels of crAssphage average nucleotide identity between related mother-infant dyads as compared to unrelated individuals, suggesting vertical transmission. We report strong positive selection in crAssphage RNA polymerase and phage tail protein genes. Finally, we demonstrate that crAssphage abundance is linearly correlated (P < 0.014) with the abundance of two bacterial taxa, Bacteroides thetaiotaomicron and Parabacteroides merdae. These results suggest that phage-bacterial interactions may help shape ecological and evolutionary dynamics in the gut.

microbiology↗