RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR activation, serves as a barrier to impede type I IFN production upon RLR activation. RLR-triggered MAVS-RIG-I recognition hijacks hexokinase binding to MAVS, leading to the impairment of hexokinase mitochondria localization and activation. Lactate serves as a key metabolite responsible for glycolysis-mediated RLR signaling inhibition by directly binding to MAVS transmembrane (TM) domain and preventing MAVS aggregation. Notably, lactate restoration reverses increased IFN production caused by lactate deficiency. Using pharmacological and genetic approaches, we show that lactate reduction by lactate dehydrogenase A (LDHA) inactivation heightens type I IFN production to protect mice from viral infection. Our study establishes a critical role of glycolysis-derived lactate in limiting RLR signaling and identifies MAVS as a direct sensor of lactate, which functions to connect energy metabolism and innate immunity.

The efficacy of an "allergen-gene immunization" protocol in altering allergic response was examined. Intramuscular injection of rats with a plasmid DNA encoding a house dust mite allergen into the muscle results in its long-term expression and the induction of specific immune responses. Significantly, this approach prevents the induction of immunoglobulin E synthesis, histamine release in bronchoalveolar fluids, and airway hyperresponsiveness in rats challenged with aerosolized allergen. Furthermore, this suppression is persistent and can be transferred into naive rats by CD8+ T cells from gene-immunized rats. These findings suggest that allergen-gene immunization is effective in modulating allergic responses, and may provide a novel therapeutic approach for allergic diseases.

Live Lactobacillus paracasi 33 (LP33) may effectively improve the quality of life for patients with perennial allergic rhinitis. It has been demonstrated that heat-killed lactic acid bacteria (LAB) suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals. The aim of this study was, therefore, to evaluate the efficacy of heat-killed LP33 in the treatment of allergic rhinitis induced by house-dust-mite in human subjects. A total of 90 patients were enrolled in a randomized, double blind, placebo-controlled trial and assigned to three treatment groups. Patients in groups A and B received two capsules per day of live or heat-killed LAB (5 x 10(9) colony-forming units/capsule), respectively, over a period of 30 days while those in Group C received placebo capsules. A modified questionnaire on pediatric rhinoconjunctivitis-related quality of life was administered to all subjects or their parents during each clinical visit. The overall quality of life score decreased for groups A and B, as compared with the placebo group, in terms of both frequency (9.47 +/- 2.89, 6.30 +/- 2.19, vs. -3.47 +/- 1.53, respectively; p < 0.0001) and level of bother (5.91 +/- 3.21, 6.04 +/- 2.44, vs. -2.80 +/- 1.64, respectively; p = 0.004) after the 30-day treatment. The efficacy of the heat-killed LP33 was not inferior to the live variant. No obvious side effects were reported for either active treatment group during the study period. Our results suggest that heat-killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis, and that it may be efficacious as an alternative treatment.