A coding variant of ANO10, affecting volume regulation of macrophages, is associated with Borrelia seropositivity

In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding Cl(−) channels and phospholipid scram-blases. ANO10 augments volume-regulated Cl(−) currents (I(Hypo)) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on I(Hypo), RVD and intracellular Ca(2+) signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection

Erythropoietin dampens injury-induced microglial motility :

Traumatic brain injury causes progressive brain atrophy and cognitive decline. Surprisingly, an early treatment with erythropoietin (EPO) prevents these consequences of secondary neurodegeneration, but the mechanisms have remained obscure. Here we show by advanced imaging and innovative analytical tools that recombinant human EPO, a clinically established and neuroprotective growth factor, dampens microglial activity, as visualized also in vivo by a strongly attenuated injury-induced cellular motility