Chlamydia trachomatis LGV (CtL2) causes systemic infection and proliferates in lymph nodes as well as genital tract or rectum producing a robust inflammatory response, presumably leading to a low oxygen environment. We therefore assessed how CtL2 growth in immortal human epithelial cells adapts to hypoxic conditions. Assessment of inclusion forming units, the quantity of chlamydial 16S rDNA, and inclusion size showed that hypoxia promotes CtL2 growth. Under hypoxia, HIF-1α was stabilized and p53 was degraded in infected cells. Moreover, AKT was strongly phosphorylated at S473 by CtL2 infection. This activation was significantly diminished by LY-294002, a PI3K-AKT inhibitor, which decreased the number of CtL2 progeny. HIF-1α stabilizers (CoCl₂, desferrioxamine) had no effect on increasing CtL2 growth, indicating no autocrine impact of growth factors produced by HIF-1α stabilization. Furthermore, in normoxia, CtL2 infection changed the NAD⁺/NADH ratio of cells with increased gapdh expression; in contrast, under hypoxia, the NAD⁺/NADH ratio was the same in infected and uninfected cells with high and stable expression of gapdh, suggesting that CtL2-infected cells adapted better to hypoxia. Together, these data indicate that hypoxia promotes CtL2 growth in immortal human epithelial cells by activating the PI3K-AKT pathway and maintaining the NAD⁺/NADH ratio with stably activated glycolysis.

沙眼衣原体LGV（CtL2）引起全身感染，并在淋巴结以及生殖道或直肠中增殖，产生强烈的炎症反应，可能导致低氧环境。因此，我们评估了永生人类上皮细胞中CtL2的生长如何适应低氧条件。评估包涵体形成单位，衣原体16S rDNA的数量和包体大小表明缺氧促进了CtL2的生长。在缺氧条件下，感染细胞中的HIF-1α稳定且p53降解。此外，AKT在S473上被CtL2感染强烈磷酸化。PI3K-AKT抑制剂LY-294002大大降低了这种激活，从而减少了CtL2后代的数量。HIF-1α稳定剂（CoCl ₂，去铁胺）对增加CtL2的生长没有影响，表明对HIF-1α稳定产生的生长因子无自分泌影响。此外，在常氧中，CtL2感染改变了gapdh表达增加的细胞的NAD ⁺ / NADH比。相比之下，在缺氧条件下，感染和未感染的细胞中NAD ⁺ / NADH比率相同，gapdh表达稳定，表明CtL2感染的细胞更适合缺氧。总之，这些数据表明缺氧通过激活PI3K-AKT途径并通过稳定激活的糖酵解维持NAD ⁺ / NADH比值来促进永生人类上皮细胞中CtL2的生长。