Antibodies acquired naturally through repeated exposure to Plasmodium falciparum are essential in the control of blood-stage malaria. Antibody-dependent functions may include neutralization of parasite–host interactions, complement activation, and activation of Fc receptor functions. A role of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in protection from malaria has not been established. Here we show that IgG isolated from adults living in a malaria-endemic region activated ADCC by primary human NK cells, which lysed infected red blood cells (RBCs) and inhibited parasite growth in an in vitro assay for ADCC-dependent growth inhibition. RBC lysis by NK cells was highly selective for infected RBCs in a mixed culture with uninfected RBCs. Human antibodies to P. falciparum antigens PfEMP1 and RIFIN were sufficient to promote NK-dependent growth inhibition. As these results implicate acquired immunity through NK-mediated ADCC, antibody-based vaccines that target bloodstream parasites should consider this new mechanism of action.

An Ixodes scapularis saliva mRNA vaccine induces tick resistance and prevents Borrelia burgdorferi infection in guinea pigs.

The world is grappling with the coronavirus disease 2019 (COVID-19) pandemic, the causative agent of which is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 symptoms are similar to the common cold, including fever, sore throat, cough, muscle and chest pain, brain fog, dyspnoea, anosmia, ageusia, and headache. The manifestation of the disease can vary from being asymptomatic to severe life-threatening conditions warranting hospitalization and ventilation support. Furthermore, the emergence of mutecated variants of concern (VOCs) is paramount to the devastating effect of the pandemic. This highly contagious virus and its emergent variants challenge the available advanced viral diagnostic methods for high-accuracy testing with faster result yields. This review is to shed light on the natural history, pathology, molecular biology, and efficient diagnostic methods of COVID-19, detecting SARS-CoV-2 in collected samples. We reviewed the gold standard RT-qPCR method for COVID-19 diagnosis to confer a better understanding and application to combat the COVID-19 pandemic. This comprehensive review may further develop awareness about the management of the COVID-19 pandemic.

As of August 6th, 2021, the World Health Organization has notified 200.8 million laboratory-confirmed infections and 4.26 million deaths from COVID-19, making it the worst pandemic since the 1918 flu. The main challenges in mitigating COVID-19 are effective vaccination, treatment, and agile containment strategies. In this review, we focus on the potential of Artificial Intelligence (AI) in COVID-19 surveillance, diagnosis, outcome prediction, drug discovery and vaccine development. With the help of big data, AI tries to mimic the cognitive capabilities of a human brain, such as problem-solving and learning abilities. Machine Learning (ML), a subset of AI, holds special promise for solving problems based on experiences gained from the curated data. Advances in AI methods have created an unprecedented opportunity for building agile surveillance systems using the deluge of real-time data generated within a short span of time. During the COVID-19 pandemic, many reports have discussed the utility of AI approaches in prioritization, delivery, surveillance, and supply chain of drugs, vaccines, and non-pharmaceutical interventions. This review will discuss the clinical utility of AI-based models and will also discuss limitations and challenges faced by AI systems, such as model generalizability, explainability, and trust as pillars for real-life deployment in healthcare.

In malaria-naïve children and adults, Plasmodium falciparum-infected red blood cells (Pf-iRBCs) trigger fever and other symptoms of systemic inflammation. However, in endemic areas where individuals experience repeated Pf infections over many years, the risk of Pf-iRBC-triggered inflammatory symptoms decreases with cumulative Pf exposure. The molecular mechanisms underlying these clinical observations remain unclear. Age-stratified analyses of uninfected, asymptomatic Malian individuals before the malaria season revealed that monocytes of adults produced lower levels of inflammatory cytokines (IL-1β, IL-6 and TNF) in response to Pf-iRBC stimulation compared to monocytes of Malian children and malaria-naïve U.S. adults. Moreover, monocytes of Malian children produced lower levels of IL-1β and IL-6 following Pf-iRBC stimulation compared to 4–6-month-old infants. Accordingly, monocytes of Malian adults produced more IL-10 and expressed higher levels of the regulatory molecules CD163, CD206, Arginase-1 and TGM2. These observations were recapitulated in an in vitro system of monocyte to macrophage differentiation wherein macrophages re-exposed to Pf-iRBCs exhibited attenuated inflammatory cytokine responses and a corresponding decrease in the epigenetic marker of active gene transcription, H3K4me3, at inflammatory cytokine gene loci. Together these data indicate that Pf induces epigenetic reprogramming of monocytes/macrophages toward a regulatory phenotype that attenuates inflammatory responses during subsequent Pf exposure. Trial Registration: ClinicalTrials.gov NCT01322581.

Tuberculosis (TB) is one of the primary causes of deaths due to infectious diseases. The current TB regimen is long and complex, failing of which leads to relapse and/or the emergence of drug resistance. There is a critical need to understand the mechanisms of resistance development. With increasing drug pressure, Mycobacterium tuberculosis (Mtb) activates various pathways to counter drug‐related toxicity. Signaling modules steer the evolution of Mtb to a variant that can survive, persist, adapt, and emerge as a form that is resistant to one or more drugs. Recent studies reveal that about 1/3rd of the annotated Mtb proteome is modified post‐translationally, with a large number of these proteins being essential for mycobacterial survival. Post‐translational modifications (PTMs) such as phosphorylation, acetylation, and pupylation play a salient role in mycobacterial virulence, pathogenesis, and metabolism. The role of many other PTMs is still emerging. Understanding the signaling pathways and PTMs may assist clinical strategies and drug development for Mtb. In this review, we explore the contribution of PTMs to mycobacterial physiology, describe the related cellular processes, and discuss how these processes are linked to drug resistance. A significant number of drug targets, InhA, RpoB, EmbR, and KatG, are modified at multiple residues via PTMs. A better understanding of drug‐resistance regulons and associated PTMs will aid in developing effective drugs against TB.