Summary Invariant natural killer T (iNKT) cells recognize glycolipids as antigens and diversify into NKT1 (IFN-γ), NKT2 (IL-4), and NKT17 (IL-17) functional subsets while developing in the thymus. Mechanisms that govern the balance between these functional subsets are poorly understood due partly to the lack of distinguishing surface markers. Here we identified the heparan sulfate proteoglycan syndecan-1 (sdc1) as a specific marker of naïve thymic NKT17 cells and that sdc1 deficiency significantly increased thymic NKT17 cells at the expense of NKT1 cells, leading to impaired iNKT cell-derived IFN-γ, both in vitro and in vivo. Using surface expression of sdc1 to identify NKT17 cells, we confirmed differential tissue localization and interstrain variability of NKT17 cells and uncovered that NKT17 cells expressed high TCRβ, preferentially use Vβ8, and display high sensitivity to ɑ-GalCer than to CD3/CD28 stimulation. These findings provide a novel non-invasive simple method for identification and viable sorting of naïve NKT17 cells from unmanipulated mice and suggest that sdc1 expression negatively regulates homeostasis iNKT cells. In addition, they lay the groundwork for investigating the mechanisms by which sdc1 regulates NKT17 cells.

Cellular interactions with engineered nanoparticles (NPs) are dependent on many properties, inherent to the nanoparticle (viz. size, shape, surface characteristics, degradation, agglomeration/dispersal, and charge, etc.). Modification of the surface reactivity via surface functionalization of the nanoparticles to be targeted seems to be important. Utilization of different surface functionalization methods of nanoparticles is an emerging field of basic and applied nanotechnology. It is well known that many disease-causing organisms induce host lipids and if deprived, their growth is inhibited in vivo. Amorphous nanosilica (ANS) and amorphous microsilica with nanopores (AMS) were prepared by a combination of wet chemistry and high-energy ball milling. Lipophilic moieties were attached to both ANS and AMS via chemical surface functionalization method. Lipophilic ANS and AMS were found to inhibit the growth of Bombyx mori nuclear polyhedrosis virus (BmNPV) and chicken malarial parasites via absorption of silkworm hemolymph and chicken serum lipids/lipoproteins, respectively, in vivo. Therefore, intelligent surface functionalization of NP is an important concept, and its application in curing chicken malaria and BmNPV is presented here. Surface functionalization method reported in this paper might serve as a valuable technology for treating many diseases where pathogens induce host lipid.

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Insects protect themselves from majority of infections by a non-specific innate immune system (present in both vertebrates and invertebrates). Bombyx mori nuclear polyhedrosis virus (BmNPV), a baculovirus, causing the deadly grasserie disease is a scourge to silkworm industry and we report here the first success in combating this disease with the help of a nanosilica-virus complex. Hydrophobic aluminium silicate nanoparticles were mixed with live BmNPV in vitro. This mixture was injected into one day old 5th instar silkworm larvae (into the hemocoel at the third abdominal spiracle) before challenging the larvae with live BmNPV via a second injection. This led to substantial enhancement of longevity in the diseased silkworm larvae and 35 +/- 5.3% larvae completed their lifecycle (i.e., formed normal pupae and enclosed as moth). On the other hand, 100% larvae infected with BmNPV alone died within 36 hours. The larvae treated with nanoparticles before infection had a longer lifespan but all of them eventually succumbed, not a single larva metamorphosed to adult stage. Results suggest two pathways of host protective response--one mediated by nanoparticlealone and the second, more important, via non-specific innate immunological mechanism. AFM and confocal studies show that nanoparticles alter 3-D molecular structure of the virus envelope. Possibly this exhibits novel potent epitope(s) which stimulate(s) anti-viral machinery in infected silkworm larvae. SDS-PAGE results suggest that 39 KDa viral protein is the major target of the nanoparticles.