CD160 Signaling Is Essential for CD8+ T Cell Memory Formation via Upregulation of 4-1BB.

A better understanding of the regulatory mechanisms governing the development of memory CD8+ T cells could provide instructive insights into vaccination strategies and T cell-based immunotherapies. In this article, we showed that CD160 surface protein is required for CD8+ T cell memory formation. In the response to acute lymphocytic choriomeningitis virus infection in a mouse model, CD160 ablation resulted in the failure of the development of all three memory CD8+ T cell subsets (central, effective, and tissue-resident memory), concomitant with a skewed differentiation into short-lived effector T cells. Such memory-related defect was manifested by a diminished protection from viral rechallenge. Mechanistically, CD160 deficiency led to downregulation of 4-1BB in activated CD8+ T cells, which contributes to the impaired cell survival and decreased respiratory capacity. The nexus between CD160 and 4-1BB was substantiated by the observation that ectopic introduction of 4-1BB was able to largely complement the loss of CD160 in memory CD8+ T cell development. Collectively, our studies discovered that CD160, once thought to be a coinhibitor of T cell signaling, is an essential promoter of memory CD8+ T cell development via activation of the costimulatory molecule 4-1BB.

ArsR Family Regulator MSMEG_6762 Mediates the Programmed Cell Death by Regulating the Expression of HNH Nuclease in Mycobacteria.

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in Mycobacterium smegmatis, an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, MSMEG_6762, leads to cell death. Transcriptome analysis revealed an increase in the genes' transcripts involved in DNA repair and homologous recombination, and in three members of HNH family DNases. Knockout of one of the DNase genes, MSMEG_1275, alleviated cell death and its over-expression of programmed cell death. Purified MSMEG_1275 cleaved the M. smegmatis DNA at multiple sites. Overall, our results indicate that the MSMEG_6762 affects cell death and is mediated, at least partially, by activation of the HNH nuclease expression under a stress condition.

Mycobacterium Von Willebrand factor protein MSMEG_3641 is involved in biofilm formation and intracellular survival.

Aim:Mycobacterium tuberculosis in vitro biofilm is associated with the virulence and persistence capability. Our aim is to delineate factors involved in biofilms development. Materials & methods: We performed transposon mutants screen and found that mutation of MSMEG_3641, a homolog of M. tuberculosis Rv1836c, can change M. smegmatis colony morphology and biofilm. Results: MSMEG_3641 contains a vWA domain that is highly conserved among Mycobacteria. The phenotypes of MSMEG_3641 mutants include disrupted biofilm, weakened migration ability and changed colony morphology. All phenotypes might be contributed to the enhanced cell wall permeability and declined cell aggregation ability. Conclusion: To our knowledge, this is the first report concerning the mycobacteria Von Willebrand factor domain function, especially in colony morphology and biofilm development.

Study of plasmonics in hybrids made from a quantum emitter and double metallic nanoshell dimer.

We developed a theory for the fluorescence (FL) for quantum emitter and double metallic nanoshell dimer hybrids using the density matrix method. The dimer is made from two identical double metallic nanoshells, which are made of a dielectric core, a gold metallic shell and a dielectric spacer layer. The quantum emitters are deposited on the surface of the spacer layers of the dimers due to the electrostatic absorptions. We consider that dimer hybrids are surrounded by biological cells. This can be achieved by injecting them into human or animal cells. The surface plasmon polaritons (SPP) are calculated for the dimer using Maxwell's equations in the static wave approximation. The calculated SPP energy agrees with experimental data from Zhai et al (2017 Plasmonics 12 263) for the dimer made from a silica core, a gold metallic nanoshell and a silica spacer layer. We have also obtained an analytical expression of the FL using the density matrix method. We compare our theory with FL experimental data from Zhai et al (2017 Plasmonics 12 263) where the FL spectrum was measured by varying the thickness of the spacer layer from 9 nm to 40 nm. A good agreement between theory and experiment is found. We have shown that the enhancement of the FL increases as the thickness of the spacer layer decreases. We have also found that the enhancement of the FL increases as the distance between the double metallic nanoshells in the dimer decreases. These are interesting findings which are consistent with the experiments of Zhai et al (2017 Plasmonics 12 263) and can be used to control the FL enhancement in the FL-based biomedical imaging and cancer treatment. These interesting findings may also be useful in the fabrication of nanosensors and nanoswitches for applications in medicine.