Heat-Killed Lactiplantibacillus plantarum DRC2509 Isolated from Kimchi Restores Immune Function After Cyclophosphamide-Induced Immunosuppression in Mice

The host immune system forms its first line of defense. Its innate effectors, including natural killer (NK) cells and macrophages, cooperate with adaptive lymphocytes to preserve immune competence. Aging, chemotherapy, and physiological stress erode this competence, creating a demand for safe dietary immunostimulants. Lactic acid bacteria are leading candidates because their cell-envelope structures engage host pattern recognition receptors. Interest has recently expanded from live probiotics to include postbiotics (inanimate cells that retain immunostimulatory activity without the constraints of live delivery). We evaluated heat-killed Lactiplantibacillus plantarum DRC2509 isolated from Korean kimchi. Ex vivo profiling of splenocytes and peritoneal macrophages (PMs) exposed to DRC2509 subjected to two heat-killing regimens identified 80 °C for 90 min as associated with dose-dependent enhancement of NK cell cytotoxicity with sustained phagocytic receptor and cytokine expression. This preparation was given orally for two weeks before cyclophosphamide challenge in mice, with β-glucan as a positive control. DRC2509 preserved body weight, thymus, and spleen indices, and restored lymphocyte and white blood cell counts. Splenic NK cytotoxicity, serum immunoglobulins A and G, mitogen-driven T and B cell proliferation, and splenocyte interleukin (IL) 2, IL6, and interferon γ secretion recovered, and PMs restored Il1β, Il6, Nos2, Cd14, Marco, and Msr1 expression. These benefits encompass both innate and adaptive immunity and manifest once host defenses are suppressed. Since heat killing preserves the strain in a stable, non-viable form without abolishing its bioactivity, DRC2509 is a food-grade candidate for supporting compromised or dysregulated immune function.