To be remembered: B cell memory response against SARS-CoV-2 and its variants in vaccinated and unvaccinated individuals.

COVID-19 disease has plagued the world economy and affected the overall well-being and life of most of the people. Natural infection as well as vaccination leads to the development of an immune response against the pathogen. This involves the production of antibodies, which can neutralize the virus during future challenges. In addition, the development of cellular immune memory with memory B and T cells provides long-lasting protection. The longevity of the immune response has been a subject of intensive research in this field. The extent of immunity conferred by different forms of vaccination or natural infections remained debatable for long. Hence, understanding the effectiveness of these responses among different groups of people can assist government organizations in making informed policy decisions. In this article, based on the publicly available data, we have reviewed the memory response generated by some of the vaccines against SARS-CoV-2 and its variants, particularly B cell memory in different groups of individuals.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

Phytochemical Screening of Nyctanthes arbor-tristis Plant Extracts and Their Antioxidant and Antibacterial Activity Analysis.

Nyctanthes arbor-tristis, alias "Vishnu Parijat," is a medicinal plant used to treat various inflammation-associated ailments and to combat innumerable infections in the traditional system of medicine. In the present study, we collected the samples of N. arbor-tristis from the lower Himalayan region of Uttarakhand, India, and carried out their molecular identification through DNA barcoding. To examine the antioxidant and antibacterial activities, we prepared the ethanolic and aqueous extracts (from flowers and leaves) and performed their phytochemical analysis by using different qualitative and quantitative approaches. The phytoextracts showed marked antioxidant potential, as revealed by a comprehensive set of assays. The ethanolic leaf extract showed marked antioxidant potential towards DPPH, ABTS, and NO scavenging (IC50 = 30.75 ± 0.006, 30.83 ± 0.002, and 51.23 ± 0.009 µg/mL, respectively). We used TLC-bioautography assay to characterize different antioxidant constituents (based on their Rf values) in the chromatograms ran under different mobile phases. For one of the prominent antioxidant spots in TLC bioautography, GC-MS analysis identified cis-9-hexadecenal and n-hexadecanoic acid as the major constituents. Furthermore, in antibacterial study, the ethanolic leaf extract showed marked activity against Aeromonas salmonicida (113.40 mg/mL of extract was equivalent to 100 µg/mL of kanamycin). In contrast, the ethanolic flower extract showed considerable antibacterial activity against Pseudomonas aeruginosa (125.85 mg/mL of extract ≡100 µg/mL of kanamycin). This study presents the phylogenetic account and unravels the antioxidant-related properties and antibacterial potential of N. arbor-tristis.

NLRP3 inflammasome drives inflammation in high fructose fed diabetic rat liver: Effect of resveratrol and metformin.

AIMS: To unravel the underlying mechanism of hepatic inflammation during type 2 diabetes (T2DM), we established the diabetic rat model by feeding with high fructose diet for twenty weeks and studied the involvement of inflammasome in the liver of these rats. MATERIALS AND METHODS: Male SD rats weighing 180-200 g were divided in four groups: 1) Control (Con group) rats were fed with corn starch diet, 2) diabetic (Dia group) rats were fed with 65% of fructose, 3) diabetic along with resveratrol (10 mg/kg/day); p.o. (Dia + Resv group) and 4) diabetic along with metformin (300 mg/kg/day); p.o. (Dia + Met group), for twenty weeks. We evaluated the establishment of T2DM in fructose fed rats and the effect of resveratrol and metformin treatment on different diabetic parameters in these rats. Further we investigated the role of NLRP3 inflammasome on T2DM induced liver inflammation and effect of resveratrol and metformin treatment on NLRP3 inflammasome driven inflammatory response. KEY FINDINGS: Rats from Dia group; manifested insulin resistance, hyperinsulinemia, hyperglycemia, elevated uric acid along with hypertriglyceridemia after fructose feeding for twenty weeks. Mostly, above parameters were attenuated in resveratrol and metformin treated groups. Expression of NLRP3 inflammasome components in liver were increased in Dia group rats with elevated transcript levels of pro-inflammatory cytokines. Histopathological examination revealed increase in glycogen content and fibrosis in Dia group rats; which was considerably reduced with resveratrol and metformin treatment. SIGNIFICANCE: Our study suggests that management of inflammation may be considered as an alternative approach to prevent liver tissue injury during chronic diabetic condition.

Antibody response patterns in chikungunya febrile phase predict protection versus progression to chronic arthritis.

Chikungunya virus (CHIKV) infection causes acute febrile illness in humans, and some of these individuals develop a debilitating chronic arthritis that can persist for months to years for reasons that remain poorly understood. In this study from India, we characterized antibody response patterns in febrile chikungunya patients and further assessed the association of these initial febrile-phase antibody response patterns with protection versus progression to developing chronic arthritis. We found 5 distinct patterns of the antibody responses in the febrile phase: no CHIKV binding or neutralizing (NT) antibodies but PCR positive, IgM alone with no NT activity, IgM alone with NT activity, IgM and IgG without NT activity, and IgM and IgG with NT activity. A 20-month follow-up showed that appearance of NT activity regardless of antibody isotype or appearance of IgG regardless of NT activity during the initial febrile phase was associated with a robust protection against developing chronic arthritis in the future. These findings, while providing potentially novel insights on correlates of protective immunity against chikungunya-induced chronic arthritis, suggest that qualitative differences in the antibody response patterns that have evolved during the febrile phase can serve as biomarkers that allow prediction of protection or progression to chronic arthritis in the future.

Host inflammatory responses to intracellular invaders: Review study.

As soon as a pathogen invades through the physical barriers of its corresponding host, host mounts a series of protective immune response to get rid of the invading pathogen. Host's pattern recognition receptors (PRR), localized at the cellular surface, cytoplasm and also in the nucleus; recognises pathogen associated molecular patterns (PAMPs) and plays crucial role in directing the immune response to be specific. Inflammatory responses are among the earliest strategies to tackle the pathogen by the host and are tightly regulated by multiple molecular pathways. Inflammasomes are multi-subunit protein complex consisting of a receptor molecule viz. NLRP3, an adaptor molecule- Apoptosis-associated speck-like protein containing a CARD (ASC) and an executioner caspase. Upon infection and/or injury; inflammasome components assemble and oligomerizes leading to the auto cleavage of the pro-caspase-1 to its active form. The activated caspase-1 cleaves immature form of the pro-inflammatory cytokines to their mature form e.g. IL1-ß and IL-18 which mount inflammatory response. Moreover, C-terminal end of the Gasdermin D molecule is also cleaved by the caspase-1. The activated N-terminal Gasdermin D molecule form pores in the infected cells leading to their pyroptosis. Hence, inflammasomes drive inflammation during infection and controls the establishment of the pathogen by mounting inflammatory response and activation of the pyroptotic cell death.

PPAR-γ and Akt regulate GLUT1 and GLUT3 surface localization during Mycobacterium tuberculosis infection.

The success of Mycobacterium tuberculosis (Mtb) as a pathogen stems from its ability to manipulate the host macrophage towards increased lipid biogenesis and lipolysis inhibition. Inhibition of lipolysis requires augmented uptake of glucose into the host cell causing an upregulation of the glucose transporters GLUT1 and GLUT3 on the cell surface. Mechanism behind this upregulation of the GLUT proteins during Mtb infection is hitherto unknown and demands intensive investigation in order to understand the pathways linked with governing them. Our endeavor to investigate some of the key proteins that have been found to be affected during Mtb infection led us to investigate host molecular pathways such as Akt and PPAR-γ that remain closely associated with the survival of the bacilli by modulating the localization of glucose transporters GLUT1 and GLUT3.

The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans.

CaGpi14 is the catalytic subunit of the first mannosyltransferase that is involved in the glycosylphosphatidylinositol (GPI) biosynthetic pathway in Candida albicans. We show that CaGPI14 is able to rescue a conditionally lethal gpi14 mutant of Saccharomyces cerevisiae, unlike its mammalian homologue. The depletion of this enzyme in C. albicans leads to severe growth defects, besides causing deficiencies in GPI anchor levels. In addition, CaGpi14 depletion results in cell wall defects and upregulation of the cell wall integrity response pathway. This in turn appears to trigger the osmotic-stress dependent activation of the HOG1 pathway and an upregulation of HOG1 as well as its downstream target, SKO1, a known suppressor of expression of hyphae-specific genes. Consistent with this, mutants of CaGPI14 are unable to undergo hyphal transformations in different hyphae-inducing media, under conditions that produce abundant hyphae in the wild-type cells. Hyphal defects in the CaGPI14 mutants could not be attributed either to reduced protein kinase C activation or to defective Ras signalling in these cells but appeared to be driven by perturbations in the HOG1 pathway. Copyright © 2016 John Wiley & Sons, Ltd.