Highlights d The nuclear matrix protein SAFA is required for antiviral immunity in cells and mice d SAFA directly senses viral RNA in the nucleus d SAFA facilitates antiviral immunity through interacting with chromatin remodelers d Oligomerized SAFA mediates IFNB1 transcription by activating its distal enhancers

Reference values for peripheral blood lymphocyte subsets of healthy children in China To the Editor: Immunophenotyping of peripheral blood lymphocyte subsets can provide important information for the diagnosis and treatment of immunological and hematological disorders. Lymphocyte compartments undergo dramatic changes during childhood; age-matched reference values derived from healthy individuals are crucial and have been evaluated in various ethnic populations. 1-5 However, extensively detailed immunophenotyping reference values of peripheral blood lymphocytes in whole spectrum of childhood are rare. Our aim was to determine the relative and absolute numbers of lymphocyte subpopulations in healthy Chinese children from birth to age 18 years. We recruited 1075 Chinese children (604 males and 471 females) who were grouped into 7 categories according to age: group 1, 0 to 28 days; group 2, 1 to 6 months; group 3, 6 to 12 months; group 4, 1 to 4 years; group 5, 4 to 8 years; group 6, 8 to 12 years; and group 7, 12 to 18 years. Whole blood was used and staining for lymphocyte surface markers was performed after red cell lysis, according to a standard flow cytometric multicolor protocol. A total of 20 subpopulations were examined: T cells (CD45 1 SSC low CD3 1), CD4 T cells (CD45 1 SSC low CD3 1 CD4 1), CD8 T cells (CD45 1 SSC low CD3 1 CD8 1), B cells (CD45 1 SSC low CD19 1), natural killer cells (CD45 1 SSC low CD3 2 CD56 1 /CD16 1), TCRab 1 double-negative T (DNT) cells TABLE I. Distribution of the percentage of total T and B cells and their subsets by age and sex in the peripheral blood of 1075 healthy children (%) Subset Sex Group 1 0-28 d (n 5 21) Group 2 1-6 mo (n 5 104) Group 3 6-12 mo (n 5 97) Group 4 1-4 y (n 5 289) Group 5 4-8 y (n 5 271) Group 6 8-12 y (n 5 158) Group 7 12-18 y (n 5 135)

Toxoplasma gondii is an important neurotropic pathogen that establishes latent infections in humans that can cause toxoplasmosis in immunocompromised individuals. It replicates inside host cells and has developed several strategies to manipulate host immune responses. However, the cytoplasmic pathogen-sensing pathway that detects T. gondii is not well-characterized. Here, we found that cyclic GMP-AMP synthase (cGAS), a sensor of foreign dsDNA, is required for activation of anti-T. gondii immune signaling in a mouse model. We also found that mice deficient in STING (Sting gt/gt mice) are much more susceptible to T. gondii infection than WT mice. Of note, the induction of inflammatory cytokines, type I IFNs, and interferon-stimulated genes in the spleen from Sting gt/gt mice was significantly impaired. Sting gt/gt mice exhibited more severe symptoms than cGAS-deficient mice after T. gondii infection. Interestingly, we found that the dense granule protein GRA15 from T. gondii is secreted into the host cell cytoplasm and then localizes to the endoplasmic reticulum, mediated by the second transmembrane motif in GRA15, which is essential for activating STING and innate immune responses. Mechanistically, GRA15 promoted STING polyubiquitination at Lys-337 and STING oligomerization in a TRAF protein-dependent manner. Accordingly, GRA15-deficient T. gondii failed to elicit robust innate immune responses compared with WT T. gondii. Consequently , GRA15 ؊/؊ T. gondii was more virulent and caused higher mortality of WT mice but not Sting gt/gt mice upon infection. Together, T. gondii infection triggers cGAS/STING signaling, which is enhanced by GRA15 in a STING-and TRAF-dependent manner. The protozoan parasite Toxoplasma gondii can infect nearly all warm-blooded animals (1, 2). As for humans, nearly 30% of the world's population is infected with T. gondii (3). In healthy adults, T. gondii is controlled by the immune system and remains dormant in the brain. However, in immunocompromised individuals, a defect of the immune system leads to the reactivation of the T. gondii parasites and the development of toxoplasmosis. Reactivated parasite replication causes life-threatening brain damage with brain abscesses and necrotic areas (4). Thus, HIV/AIDS patients, cancer patients, and organ transplant recipients are highly susceptible to T. gondii infection. The infection of T. gondii parasites is recognized by pattern recognition receptors (PRRs). 4 Previous studies showed that TLR11 is the PRR of T. gondii in murine cells. TLR11 is able to detect the actin-binding protein Profilin, which is required for entry of T. gondii during infection. TLR11 and TLR12 form a heterodimer in murine dendritic cells (DC) after sensing Profilin and activate adaptor protein MyD88 to initiate downstream signaling for defense against T. gondii (5). Moreover, TLR7 and TLR9 are able to compensate for the loss of TLR11 by activating

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Highlights d Mitochondrial protein ERAL1 positively regulates RNA virustriggered innate immunity d ERAL1 can translocate from mitochondria to cytoplasm after viral infection d ERAL1 is released through the BAX/BAK pore in a RIG-I-and MDA5-dependent manner d ERAL1 mediates polyubiquitination and activation of RIG-I and MDA5