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Membrane ion channels of the calcium homeostasis modulator (CALHM) family promote cell–cell crosstalk at neuronal synapses via ATP release, where ATP acts as a neurotransmitter. CALHM6, the only CALHM highly expressed in immune cells, has been linked to the induction of natural killer (NK) cell anti‐tumour activity. However, its mechanism of action and broader functions in the immune system remain unclear. Here, we generated Calhm6−/− mice and report that CALHM6 is important for the regulation of the early innate control of Listeria monocytogenes infection in vivo. We find that CALHM6 is upregulated in macrophages by pathogen‐derived signals and that it relocates from the intracellular compartment to the macrophage‐NK cell synapse, facilitating ATP release and controlling the kinetics of NK cell activation. Anti‐inflammatory cytokines terminate CALHM6 expression. CALHM6 forms an ion channel when expressed in the plasma membrane of Xenopus oocytes, where channel opening is controlled by a conserved acidic residue, E119. In mammalian cells, CALHM6 is localised to intracellular compartments. Our results contribute to the understanding of neurotransmitter‐like signal exchange between immune cells that fine‐tunes the timing of innate immune responses. Synopsis: CALHM6 is an immune synaptic ion channel that regulates the kinetics of natural killer (NK) cell activation during infection.Pro‐inflammatory stimuli like Poly(I:C) and systemic Listeria monocytogenes infection activate macrophages to upregulate CALHM6 expression.Infected macrophages activate NK cells in the spleen through the formation of an immunological synapse to which CALHM6 is recruited.In Calhm6‐deficient mice infected with L. monocytogenes, the production of IFN‐γ and IL‐10 from NK cells is delayed and the initial bacterial burden increased.Mouse CALHM6 expression in the membrane of Xenopus oocytes is toxic as the channel is constitutively open. Cells with reduced or transient mCALHM6 expression generate ion currents dependent on the conserved negatively charged residue E119. [ABSTRACT FROM AUTHOR]

Objective: To comprehensively investigate the effects of 25 variants in 15 genes on dental caries susceptibility in a cohort of Chinese children. Methods: A total of 25 variants in 15 genes were genotyped with MassARRAY iPLEX system and analyzed in 265 healthy controls and 254 children affected by dental caries with different dmft scores. The children with dental caries were stratified into "mild group" (scores from 1 to 3), "moderate group" (scores from 4 to 6), and "severe group" (scores from 7 to 14). Results: The association analysis revealed that rs11362 of defensin β1 (DEFB1) was significantly associated with dental caries susceptibility (OR = 2.447, p = 1.165E−04). Furthermore, rs11362 was positively correlated with the severity of dental caries. For another selected variant of DEFB1, rs1799946 was significantly associated with dental caries susceptibility in the severe group (OR = 0.473, p = 3.70E−03) and also significant in the group consisted of moderate and severe subjects (OR = 0.623, p =.033). The results from logistic regression in additive, dominant, and recessive models also exhibited the similar patterns. Conclusion: Out of 25 selected variants, only 2 of DEFB1 gene (rs11362 and rs1799946) were significantly associated with dental caries susceptibility in children. [ABSTRACT FROM AUTHOR]

CALHM1 was recently demonstrated to be a voltage-gated ATP-permeable ion channel and to serve as a bona fide conduit for ATP release from sweet-, umami-, and bitter-sensing type II taste cells. Calhm1 is expressed in taste buds exclusively in type II cells and its product has structural and functional similarities with connexins and pannexins, two families of channel protein candidates for ATP release by type II cells. Calhm1 knockout in mice leads to loss of perception of sweet, umami, and bitter compounds and to impaired gustatory nerve responses to these tastants. These new studies validate the concept of ATP as the primary neurotransmitter from type II cells to gustatory neurons. Furthermore, they identify voltage-gated ATP release through CALHM1 as an essential molecular mechanism of ATP release in taste buds. We discuss these new findings, as well as unresolved issues in peripheral taste signaling that we hope will stimulate future research. [ABSTRACT FROM AUTHOR]