A recent study demonstrated that GPR65, a sensor of extracellular pH (pHe), regulates adaptive immune response and tissue inflammation in mice models of inflammatory and infectious diseases,39 and another study considered that GPR65 partially explains the regulation of IL-6 and TNF-α in macrophages under acidic microenvironments.40 Unexpectedly, we found that H89, an inhibitor of GPR-cAMP-PKA signaling, did not affect the anti-inflammatory activity of L-malate supplementation (Supplementary Fig. 4c) in LPS-stimulated macrophages. Here, TNF is linked to infectious disease.