Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice

T Follicular Helper (Tfh) cells are an independent CD4+&#160;T cell subset specialized in providing help for germinal center (GC) development and ...

University of Chinese Academy of Sciences

Somatic cells can be reprogrammed to neurons and various other cell types with retrovirus or lentivirus. The limitation of this technology is that these genome-integration viruses may increase the risk of gene mutation and cause insertional mutagenesis. We recently found that non-integration adenovirus carrying neuronal transcription factors can induce fibroblasts to neurons. However, the conversion efficiency by the adenovirus is lower than that of the retrovirus or lentivirus. Therefore, it is crucial to identify other factors or chemical compounds to obtain neurons with high efficiency. In this study we show that the combination of Rarg (retinoic acid receptor γ) and Nr5a2 (nuclear receptor subfamily 5, group A, member 2; also known as Lrh-1 (liver receptor homologue 1)) rapidly promote the iN cell maturation within 1 week and greatly facilitate the conversion with neuronal purities of ∼50% and yields of >130%. They also improve neuronal pattern formation, electrophysiological characteristics, and functional integration in vivo. Moreover, the chemical compound agonists to Rarg and Nr5a2 function effectively as well. This approach may be used for the generation and application of iN cells in regenerative medicine. 

Retinoic acid receptor γ (Rarg) and nuclear receptor subfamily 5, group A, member 2 (Nr5a2) promote conversion of fibroblasts to functional neurons.

The dynamics of leaf nitrogen (N) and phosphorus (P) have been intensively explored in short-term experiments, but rarely at longer timescales. Here, we investigated leaf N : P stoichiometry over a 27-year interval in an Inner Mongolia grassland by comparing leaf N : P concentration of 2006 with that of 1979. Across 80 species, both leaf N and P increased, but the increase in leaf N lagged behind that of leaf P, leading to a significant decrease in the N : P ratio. These changes in leaf N : P stoichiometry varied among functional groups. For leaf N, grasses increased, woody species tended to increase, whereas forbs showed no change. Unlike leaf N, leaf P of grasses and forbs increased, whereas woody species showed no change. Such changes may reflect N deposition and P release induced by soil acidification over the past decades. The interannual effect of precipitation may somewhat have reduced the soil available N, leading to the more modest increase of leaf N than of leaf P. Thus, leaf N : P stoichiometry significantly responded to long-term environmental changes in this temperate steppe, but different functional groups responded differently. Our results indicate that conclusions of plant stoichiometry under short-term N fertilization should be treated with caution when extrapolating to longer timescales. 

Leaf P increase outpaces leaf N in an Inner Mongolia grassland over 27 years.

Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded by ) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorate  and lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChRCD11b cells (CD11b is coded by , a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury. Using both  and LPS-induced lung injury mouse models, we found that vagotomy augmented splenic egress and lung recruitment of α7 nAChRCD11b cells, and consequently worsened lung inflammatory responses. Rescue of vagotomy with an α7 nAChR agonist preserved α7 nAChRCD11b cells in the spleen, suppressed recruitment of these cells to the lung and attenuated lung inflammatory responses. Vagal signals via α7 nAChR promoted serine473 phosphorylation of AKT1 in α7 nAChRCD11b cells and stabilized these cells in the spleen. Deletion of  enhanced splenic egress and lung recruitment of α7 nAChRCD11b cells, which elicited neutrophil-infiltrated lung inflammation and injury. Vagotomy and double deletion of  and  reduced serine473 phosphorylation of AKT1 in the spleen and BAL (bronchoalveolar lavage) Ly6CGr1 neutrophils and Ly6C monocytes, and they facilitated the recruitment of neutrophils and monocytes to the airspaces of injured lungs. Double deletion of  and  increased lung recruitment of monocytes and/or neutrophils and deteriorated  and LPS-induced lung injury. Thus, signals of vagal circuits engaging with AKT1 in α7 nAChRCD11b cells attenuate  and LPS-induced acute lung inflammatory responses. Targeting this signaling pathway could provide novel therapeutic strategies for treating acute lung injury.

Signals of vagal circuits engaging with AKT1 in α7 nAChRCD11b cells lessen  and LPS-induced acute inflammatory injury.

The patchy distribution of vegetation in dry land results in well-documented "fertile islands". However, the response of shrub fertile islands to plant recovery and the underlying mechanisms, such as the linkage plant and soil properties, remain unknown. We sampled soils from areas with three different plant coverages (25%, 45%, and 75%) and three of their adjacent inter-plants to investigate soil physicochemical and microbial properties in the upper Minjiang River arid valley. The results showed that these factors were influenced by the persistence of plants that contrasted with the inter-plant interspaces. We found fertile islands in under-plant soil that were enhanced with increasing plant coverage, from 25% to 45% and 75%; however, there were no significant differences between 45% and 75% plant coverage apart from the soil clay content and the fungi to bacteria ratio. The soil microbial communities in under-plant soil were strongly influenced by the total soil carbon (TC), soil organic carbon (SOC), and available nitrogen (AN), whereas the microbial communities in inter-plant soil were primarily constrained by the AN and available phosphorous (AP). Moreover, the inter-plant soil properties, including gravimetric soil water content, pH, electrical conductivity (EC), and soil C:N ratio, were also strongly influenced by adjacent vegetation, which suggested that fertile islands may be beneficial for plant recovery in this region.

Effects of plant coverage on shrub fertile islands in the Upper Minjiang River Valley.

Induction of long-lived antibody responses during infection or vaccination is often essential for subsequent protection, but the relative contributions of T follicular helper (Tfh) cells and T helper 1 (Th1) cells for induction of antigen specific antibody responses to viruses are unclear. Here, we establish an acute Zika virus (ZIKV) infection model in immunocompetent mice, and show that ZIKV infection elicits robust Th1-like Tfh cell and protective antibody responses. While these Th1-like Tfh cells share phenotypic and transcriptomic profiles with both Tfh and Th1 cells, they also have unique surface markers and gene expression characteristics, and are dependent on T-bet for their development. Th1-like Tfh cells, but not Th1 cells, are essential for class switching of ZIKV-specific IgG2c antibodies and maintenance of long-term neutralizing antibody responses. Our study suggests that specific modulation of the Th1-like Tfh cell response during infection or vaccination may augment the induction of antiviral antibody response to ZIKV and other viruses.

ZIKV infection induces robust Th1-like Tfh cell and long-term protective antibody responses in immunocompetent mice.

Major depressive depression (MDD) is often accompanied by suicidal behavior. Increasing evidence shows that MDD patients display psychotic symptoms. However, the relationship between psychotic symptoms and suicide attempt in MDD has not been reported. Therefore, this study was to identify the prevalence and associated factors of suicide attempts in first-episode and untreated Chinese Han outpatients comorbid with psychotic major depression (PMD).

Yuanyuan Huang

CAS Key Laboratory of Molecular Virology and Immunology,
Institut Pasteur of Shanghai,
Chinese Academy of Sciences,
CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences

University of Chinese Academy of Sciences

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice