Divergent innate and adaptive immune trajectories after bariatric surgery in people with severe obesity

Background Obesity disrupts type 2 immune cell populations in white adipose tissue, replacing the homeostatic network of group 2 innate lymphoid cells (ILC2s), eosinophils, T helper 2 (Th2) cells, and alternatively activated macrophages (AAMs) with pro-inflammatory type 1 populations. Whether this remodelling reflects permanent immune impairment or a reversible shift in cellular equilibrium, and to what extent bariatric surgery restores type 2 immunity, remain incompletely understood. Methods We analysed selected type 2 immune cell populations in visceral white adipose tissue (WAT) and peripheral blood from persons with severe obesity (people with obesity, PWO) scheduled for or having undergone bariatric surgery (sleeve gastrectomy, gastric bypass), as well as non-obese controls. Using flow cytometry, quantitative PCR, and in vitro polarization assays, we assessed immune cell frequencies, transcription factor expression, cytokine profiles, and functional polarization capacity across lean, pre-operative, and post-operative states. Results Obesity was associated with decreased eosinophil and CD8 + T cells frequencies in WAT, accompanied by an increase in CD4 + frequency and a shift from Th2 toward Th1 predominance, as well as elevated PD-1 expression on T cell subsets. PWO after bariatric surgery showed reduced CD8 + T cell frequencies and increased CD4 + T cells compared to lean controls. Macrophage polarization capacity was increased in PWO after surgery compared to pre-operative PWO. Conversely, Th2 polarization capacity and IL-13 production were reduced in T cells from post-operative PWO despite no detectable impairment pre-operatively, consistent with divergent innate and adaptive immune profiles after surgery. Conclusion Type 2 immune cells showed no detectable loss of functional plasticity in human obesity despite reduced frequency. PWO after bariatric surgery show differentially reconstituted immune function, with greater macrophage plasticity and a trend towards reduced Th2 polarization capacity, despite higher GATA3 protein levels compared to PWO without bariatric surgery, arguing against uniform immune normalisation after weight loss.