Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants

Background The immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories. Methods The neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination. Findings The Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions Immune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants. Funding This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).

Sugar-rich larval diet promotes lower adult pathogen load and higher survival after infection in a polyphagous fly

Nutrition is a central factor influencing immunity and resistance to infection, but the extent to which nutrition during development affects adult responses to infections is poorly understood. Our study investigated how the nutritional composition of the larval diet affects the survival, pathogen load, and food intake of adult fruit flies, Bactrocera tryoni, after bacterial septic infection. We found a sex-specific effect of larval diet composition on survival post-infection: survival rate was higher and bacterial load was lower for infected females fed sugar-rich larval diet compared with females fed protein-rich larval diet, an effect that was absent in males. Both males and females were heavier when fed a balanced larval diet compared to protein- or sugar-rich diet, while body lipid reserves were higher in the sugar-rich larval diet compared with other diets. Body protein reserve was lower for sugar-rich larval diets compared to other diets in males, but not females. Both females and males shifted their nutrient intake to ingest a sugar-rich diet when infected compared with sham-infected flies without any effect of the larval diet, suggesting that sugar-rich diets can be beneficial to fight off bacterial infection. Overall, our findings show that nutrition during early life can shape individual fitness in adulthood.

NITROGEN LIMITATION ADAPTATION functions as a negative regulator of Arabidopsis immunity

Background: Phosphorus is an important macronutrient required for plant growth and development. It is absorbed through the roots in the form of inorganic phosphate (Pi). To cope with Pi limitation, plants have evolved an array of adaptive mechanisms to facilitate Pi acquisition and protect them from stress caused by Pi starvation. The NITROGEN LIMITATION ADAPTION (NLA) gene plays a key role in the regulation of phosphate starvation responses (PSR), its expression being regulated by the microRNA miR827. Stress caused by Pi limiting conditions might also affect the plant response to pathogen infection. However, cross-talk between phosphate signaling pathways and immune responses remains unclear. Results: In this study, we investigated whether NLA plays a role in Arabidopsis immunity. We show that loss-of-function of NLA and MIR827 overexpression causes an increase in phosphate (Pi) content which results in resistance to infection by the fungal pathogen Plectosphaerella cucumerina. The nla mutant plants accumulated callose in their leaves, a response that is also observed in wild-type plants that have been treated with high Pi. We also show that pathogen infection and treatment with fungal elicitors is accompanied by transcriptional activation of MIR827 and down-regulation of NLA. Upon pathogen challenge, nla plants exhibited higher levels of the phytoalexin camalexin compared to wild type plants. Camalexin level also increases in wild type plants treated with high Pi. Furthermore, the nla mutant plants accumulated salicylic acid (SA) and jasmonic acid (JA) in the absence of pathogen infection whose levels further increased upon pathogen. Conclusions: This study shows that NLA acts as a negative regulator of Arabidopsis immunity. Overaccumulation of Pi in nla plants positively affects resistance to infection by fungal pathogens. This piece of information reinforces the idea of signaling convergence between Pi and immune responses for the regulation of disease resistance in Arabidopsis.

Phosphate-induced resistance to pathogen infection in Arabidopsis

In nature, plants are concurrently exposed to a number of abiotic and biotic stresses. Our understanding of convergence points between responses to combined biotic/abiotic stress pathways remains, however, rudimentary. Here we show that MIR399 overexpression, loss-of-function of PHO2 (PHOSPHATE2), or treatment with high Pi, is accompanied by an increase in phosphate (Pi) content and accumulation of reactive oxygen species (ROS) in Arabidopsis thaliana. High Pi plants (e.g. miR399 overexpressor, pho2 mutant, and plants grown under high Pi supply) exhibited resistance to infection by necrotrophic and hemibiotrophic fungal pathogens. In the absence of pathogen infection, the expression level of genes in the salicylic acid (SA)- and jasmonic acid (JA)-dependent signaling pathways was higher in high Pi plants compared to wild type plants, which is consistent with increased levels of SA and JA in non-infected high Pi plants. During infection, an opposite regulation in the two branches of the JA pathway (ERF1/PDF1.2 and MYC2/VSP2) occurs in high Pi plants. Thus, while the ERF1-PDF1 branch positively responds to fungal infection, the MYC2/VSP2 branch is negatively regulated during pathogen infection in high Pi plants. This study supports that Pi accumulation promotes resistance to infection by fungal pathogens in Arabidopsis, while providing a basis to better understand crosstalk between Pi signaling and hormonal signalling pathways for modulation of plant immune responses.

Heparin-Induced Fever in Neurointensive Care Unit: A Rarity Yet a Possibility

Fever is considered a protective response having multitude of benefits in terms of enhancing resistance to infection, recruiting cytokines to the injured tissue, and promoting healing. In terms of an injured brain, this becomes a double-edged sword triggering an inflammatory cascade resulting in secondary brain injury. It is important to identify the etiology so that corrective measures can be taken. Here we report a case of persistent fever in a patient with Guillain-Barré syndrome, which was probably due to heparin. This is the first report of heparin-induced fever in a neurocritical care setting and third report overall.

Boesenbergia pandurata application in Goldfish (Cyprinus carpio) Feed to Enhancing Fish Growth, Immunity System, and Resistance to Bacterial Infection

Background: This study investigated how the inclusion of Boesenbergia pandurata extract (BPE) in goldfish feed affects fish growth, immunity, and resistance to infection by Aeromonas hydrophila and Pseudomonas fluorescens. Methods: Four fish feeds, were prepared by adding BPE at the concentrations of 0 (control), 2, 4, and 6 g kg-1, respectively, and 120 goldfish (Cyprinus carpio; initial weight 5 g) were separated into 12 boxes and fed with specific pellets and examined thrice. The experiment lasted 12 weeks, beginning with the different feeds, fish growth was measured at Weeks 4 and 8 after the feeding period. Moreover, a challenge test with pathogen bacteria to assay disease resistance was administered at Week 8 after the feeding period, and the survival rate and relative percentage of survival were quantified at Week 12. Results: At Week 8, the goldfish that were fed BPE-containing feeds were significantly heavier than the fish that received the control feed (pellet without BPE), and the highest weight gain, reaching 72.44 g, was obtained with Pellet 3; accordingly, the specific growth rate after BPE treatment (5.7%) was higher than that after control treatment. Conversely, the feed conversion ratio in the control group, 2.03, was higher than the ratios in the BPE groups, which were decreased to 0.55–0.90. Lastly, BPE treatment consistently enhanced the immunity parameters of goldfish (relative to control treatment) at weeks 4 and 8, and following BPE treatment, the rate of resistance against bacterial infection, 68.3%–77.0%, was higher than that after control treatment. Conclusions: BPE addition in goldfish feed clearly produces a positive effect by enhancing fish growth, immunity, and resistance to infection by pathogenic bacteria, and 4 g kg-1 is the optimal BPE concentration in feed prepared for goldfish.

Advances on the Role and Applications of Interleukin-1 in Tuberculosis

Interleukin-1 (IL-1) is a key player in the immune response to pathogens due to its role in promoting inflammation and recruiting immune cells to the site of infection. In tuberculosis (TB), tight regulation of IL-1 responses is critical to ensure host resistance to infection while preventing immune pathology.

Diverse pathogens activate the host RIDD pathway to subvert BLOS1-directed immune defense

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α- dependent decay (RIDD) of mRNAs encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Non-functional Blos1 struggled to assemble the BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Blos1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal-destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus MHV also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.

Bioengineered Acellular Vessel Implantation in a Patient with Chronic Limb-Threatening Ischemia: A Case Report and Discussion of Implications for Trauma

The ideal conduit for vascular reconstruction is one that can be obtained “off the shelf” and demonstrates long-term patency, tissue incorporation and resistance to infection. Currently available conduits, such as autologous vein and synthetic grafts, are limited in one or more of these areas. The Human Acellular Vessel (HAV), a bioengineered, acellular blood vessel, can be obtained “off the shelf” and has shown promise in each of these properties. We describe a case in which the HAV was utilized for open bypass reconstruction in a patient with chronic limb-threatening ischemia who lacked alternative reconstructive options. The case is followed by a discussion of potential broader applications of this novel implant, specifically in the management of vascular trauma.