Erratum: Author Correction: Role of innate lymphoid cells and dendritic cells in intradermal immunization of the enterovirus antigen.

[This corrects the article DOI: 10.1038/s41541-019-0108-6.].

Role of innate lymphoid cells and dendritic cells in intradermal immunization of the enterovirus antigen.

Enterovirus type 71 (EV71) and coxsackievirus A 16 (CA16) are the major pathogens of human hand, foot, and mouth disease (HFMD). In our previous study, intramuscular immunization with the inactivated EV71 vaccine elicited effective immunity, while immunization with the inactivated CA16 vaccine did not. In this report, we focused on innate immune responses elicited by inactivated EV71 and CA16 antigens administered intradermally or intramuscularly. The distributions of the EV71 and CA16 antigens administered intradermally or intramuscularly were not obviously different, but the antigens were detected for a shorter period of time when administered intradermally. The expression levels of NF-κB pathway signaling molecules, which were identified as being capable of activating DCs, ILCs, and T cells, were higher in the intradermal group than in the intramuscular group. Antibodies for the EV71 and CA16 antigens colocalized with ILCs and DCs in skin and muscle tissues under fluorescence microscopy. Interestingly, ILC colocalization decreased over time, while DC colocalization increased over time. ELISpot analysis showed that coordination between DCs and ILCs contributed to successful adaptive immunity against vaccine antigens in the skin. EV71 and/or CA16 antigen immunization via the intradermal route was more capable of significantly increasing neutralizing antibody titers and activating specific T cell responses than immunization via the intramuscular route. Furthermore, neonatal mice born to mothers immunized with the EV71 and CA16 antigens were 100% protected against wild-type EV71 or CA16 viral challenge. Together, our results provide new insights into the development of vaccines for HFMD.

Immune mechanisms induced by an HSV-1 mutant strain: Discrepancy analysis of the immune system gene profile in comparison with a wild-type strain.

Herpes simplex virus is a prevalent pathogen of humans of various age groups. The fact that no prophylactic or therapeutic vaccine is currently available suggests a significant need to further investigate the immune mechanisms induced by the virus and various vaccine candidates. We previously generated an HSV-1 mutant strain, M3, with partial deletions in ul7, ul41 and LAT that produced an attenuated phenotype in mice. In the present study, we performed a comparative analysis to characterize the immune responses induced by M3 versus wild-type HSV-1 in a mouse model. Infection with wild-type HSV-1 triggered an inflammatory-dominated response and adaptive immunity suppression and was accompanied by severe pathological damage. In contrast, infection with M3 induced a systematic immune response involving full activation of both innate and adaptive immunity and was accompanied by no obvious pathological changes. Furthermore, the immune response induced by M3 protected mice from lethal challenge with wild-type strains of HSV-1 and restrained virus proliferation and impaired latency. These data are useful for further HSV-1 vaccine development using a mutant strain construction strategy.

Disruption of Gen1 Causes Congenital Anomalies of the Kidney and Urinary Tract in Mice.

Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common developmental defects in humans. Despite of several known CAKUT-related loci (HNF1B, PAX2, EYA1, etc.), the genetic etiology of CAKUT remains to be elucidated for most patients. In this study, we report that disruption of the Holliday Junction resolvase gene Gen1 leads to renal agenesis, duplex kidney, hydronephrosis, and vesicoureteral reflux (VUR) in mice. GEN1 interacts with SIX1 and enhances the transcriptional activity of SIX1/EYA1, a key regulatory complex of the GDNF morphogen. Gen1 mutation impairs Grem1 and Gdnf expression, resulting in excessive ureteric bud formation and defective ureteric bud branching during early kidney development. These results revealed an unidentified role of GEN1 in kidney development and suggested its contribution to CAKUT.

Protective Effects of Coenzyme Q10 Against Hydrogen Peroxide-Induced Oxidative Stress in PC12 Cell: The Role of Nrf2 and Antioxidant Enzymes.

Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. Coenzyme Q10 (CoQ10), an essential component in the mitochondrial respiratory chain, has recently gained attention for its potential role in the treatment of neurodegenerative disease. Here, we investigated the possible protective effects of CoQ10 on H2O2-induced neurotoxicity in PC12 cells and the underlying mechanism. CoQ10 showed high free radical-scavenging activity as measured by a DPPH and TEAC. Pre-treatment of cells with CoQ10 diminished intracellular generation of ROS in response to H2O2. H2O2 decreased viability of PC12 cells which was reversed by pretreatment with CoQ10 according to MTT assay. H2O2-induced lipid peroxidation was attenuated by CoQ10 as shown by inhibition of MDA formation. Furthermore, pre-incubation of the cells with CoQ10 also restored the activity of cellular antioxidant enzymes which had been altered by H2O2. Moreover, CoQ10 induced Nrf2 nuclear translocation, the upstream of antioxidant enzymes. These findings suggest CoQ10 augments cellular antioxidant defense capacity through both intrinsic free radical-scavenging activity and activation of Nrf2 and subsequently antioxidant enzymes induction, thereby protecting the PC12 cells from H2O2-induced oxidative cytotoxicity.

MitoRCA-seq reveals unbalanced cytocine to thymine transition in Polg mutant mice.

Mutations in mitochondrial DNA (mtDNA) can lead to a wide range of human diseases. We have developed a deep sequencing strategy, mitoRCA-seq, to detect low-frequency mtDNA point mutations starting with as little as 1 ng of total DNA. It employs rolling circle amplification, which enriches the full-length circular mtDNA by either custom mtDNA-specific primers or a commercial kit, and minimizes the contamination of nuclear encoded mitochondrial DNA (Numts). By analyzing the mutation profiles of wild-type and Polg (mitochondrial DNA polymerase γ) mutant mice, we found that mice with the proofreading deficient mtDNA polymerase have a significantly higher mutation load by expanding the number of mutation sites and to a lesser extent by elevating the mutation frequency at existing sites even before the premature aging phenotypes appear. Strikingly, cytocine (C) to thymine (T) transitions are found to be overrepresented in the mtDNA of Polg mutated mice. The C → T transition, compared to other types of mutations, tends to increase the hydrophobicity of the underlying amino acids, and may contribute to the impaired protein function of the Polg mutant mice. Taken together, our findings may provide clues to further investigate the molecular mechanism underlying premature aging phenotype in Polg mutant mice.