Metabolic reprogramming, macrophage polarization, and intercellular crosstalk in pelvic inflammatory disease: emerging paradigms and therapeutic opportunities

Pelvic inflammatory disease (PID) is a condition caused by the ascension of pathogenic microorganisms from the lower genital tract to the uterus and/or fallopian tubes, and is one of the most common clinical syndromes among women of reproductive age. The long-term sequelae of PID, including chronic pelvic pain, infertility, and recurrent episodes, significantly impair patients’ quality of life. However, the current clinical understanding of the immunopathological mechanism of PID remains insufficient, and there are no targeted therapeutic approaches. In recent years, macrophage polarization has been demonstrated to play a core regulatory role in the initiation, progression, and resolution of inflammation, and metabolic reprogramming is the key intrinsic mechanism driving the phenotypic transformation of macrophages, playing a crucial role in various diseases. At the same time, the bidirectional communication network between macrophages and endometrial cells has also been proven to play an important role in the disease progression. Therefore, clarifying the metabolic adaptation mechanism regulating macrophage polarization and its interaction with endometrial cells can provide potential targets for exploring new therapeutic strategies that target macrophage metabolism or block abnormal cell communication, which is crucial for developing targeted treatments that can restore immune homeostasis and alleviate the pathological damage of PID.