Ever wondered how the phage λ Red recombination system resembles the Red Queen? Hossain et al. (2021) provide an answer in this issue of Cell Host & Microbe. They show that Red debilitates PAM sequences by mutagenic repair of CRISPR-targeted DNA breaks in infecting λ, thus shaping the phage-CRISPR arms race.

Auxin secreted by root-associated bacteria promotes plant growth, yet benefits to bacteria themselves are ill-defined. In this issue of Cell Host & Microbe, Tzipilevich et al. (2021) demonstrate that auxin and plant EFR-triggered response are essential for root colonization of B. velezensis, indicating potential co-evolution of plants and root commensal bacteria.

Shigella is a highly infectious human pathogen, yet mice are naturally resistant to infection. In this issue of Cell Host & Microbe, Luchetti et al. (2021) discuss this species specificity, demonstrating that Shigella directly targets the pore-forming protein Gasdermin D for degradation, thus preventing pyroptosis to enable infection of human cells.

In this issue of Cell Host & Microbe, Seki et al. (2021) demonstrate an overgrowth of Klebsiella in the gut microbiota of extremely premature infants that is predictive of brain damage. The Klebsiella-associated pro-inflammatory signature suggests that aberrant microbiome-gut-brain axis signaling provokes the disruption of neurodevelopmental trajectories to exacerbate brain injury.

The development of colorectal cancer has been predicted to inolve the enteric microbiome. In this issue of Cell Host & Microbe, Kordahi et al. (2021) address this predisposition by identifying not just pathobiont micro-organisms but also distinct microbial signatures within those bacteria that predict the presence of pre-cancerous polyps.

SARS-CoV-2 has mutually illuminated our collective knowledge and knowledge gaps, particularly in antiviral defense and therapeutic strategies. A recent study in Science (Poirier et al., 2021) uncovers an ancient antiviral mechanism that mammals utilize to suppress viruses, including SARS-CoV-2 and Zika virus, that could have broad implications for therapeutic strategies.

Endogenous peptides and structurally similar bacterial heat-stable enterotoxins (ST) bind guanylate cyclase-C (GC-C), resulting in fluid homeostasis or diarrhea, respectively. In this issue of Cell Host & Microbe, Carey et al., show how bats have evolutionarily maintained homeostatic signaling while avoiding pathogenic effects of ST.

In this issue of Cell Host & Microbe, Brown et al. reveal a large group of genes within the human microbiome that code for ADP-ribosyltransferases that are predicted to manipulate host cells. Previously studied for pathogens, these host modification mechanisms may also be common properties of commensals.

RNAi is a major plant antiviral strategy. However, the mechanisms triggering RNAi are unknown. In this issue of Cell Host & Microbe, Wang et al. (2021) demonstrate that wound-induced calcium signaling induces RNAi activation. As a counter-defense, a viral suppressor of RNAi (VSR) interferes with players in calcium signaling.

A recent study in Nature finds significant shifts in the gut microbiome of post-menopausal women on severe calorie restriction concomitant with weight loss. Microbiota transplantation to germ-free mice display a similar weight loss, along with a bloom in C. difficile, unlocking clues to microbial metabolic alteration in weight loss.

In this issue of Cell Host and Microbe, Robinson et al. (2021) make elegant use of experimental evolution to demonstrate that increased motility promotes migration toward and colonization of zebrafish larvae by a commensal bacterium. Stimulation of motility depends on bacterial second messenger and on signals released by resident host microbiota.

The skin barrier is critical in ensuring homeostasis, yet factors influencing its development, repair, and maintenance are ill-defined. In this issue of Cell Host & Microbe, Uberoi et al. demonstrate the skin microbiota’s role in maintaining barrier integrity via AHR signaling in keratinocytes, which has implications for skin disease management.

Engagement of LC3-associated phagocytosis (LAP) in response to the uptake of certain particles modulates innate immune responses. Now in Cell Host and Microbe, Akoumianaki et al. (2021) show how a regulatory role of IL-6 on LAP may be at the core of susceptibility to secondary infection during severe sepsis.

The spectrum of gut microbiome composition is readily but controversially distilled into a handful of community types. In this issue of Cell Host & Microbe, Lee et al. (2021) find that matching pre-existing community types (and associated molecular biomarkers) to the class of immune biologic therapy in inflammatory bowel disease may double the treatment response.

The likely animal source of SARS-CoV-2 remains speculative. A recent study published in Cell by Zhou et al. reported the detection of novel alpha- and betacoronaviruses, including SARS-CoV-2-related viruses in bats.

Mounting a robust immune response against SARS-CoV-2 requires neutralization as well as effector T cell functions. In this issue of Cell Host Microbe, Tauzin et al. characterize the humoral and T cell responses after a single dose of BNT162b2 mRNA vaccine in individuals with or without previous exposure to SARS-CoV-2.

Global vaccine inequity is prolonging the COVID-19 pandemic. Here, we outline the scope and impact of inequitable vaccine distribution and identify challenges in vaccine development, manufacturing, and distribution as well as potential solutions to address this crisis.

A previously immune-naive world population is experiencing natural infection with SARS-CoV-2. Severe COVID-19 predominantly impacts adults, yet multisystem inflammatory disorder primarily impacts children. Herein, we discuss known clinical and biological features of SARS-CoV-2 in children and reflect on currently identified immune features and discuss what remains unknown.

Severe COVID-19 arises from the convergence of inadequate pre-existing immunity and a host response that damages, rather than repairs, tissues. We outline clinical presentations of COVID-19 that are likely driven by dysregulated host immunity, discuss potential mechanisms underlying pathological responses, and highlight important areas for basic research on this topic.

If enough individuals in a population are immune to a pathogen, it cannot cause an outbreak. Deliberately seeking such herd immunity through infection during a potentially lethal pandemic is contrary to all principles of public health, given the potential for uncontrolled outbreaks and risks to vulnerable populations.

COVID-19 can result in severe disease characterized by significant immunopathology that is spurred by an exuberant, yet dysregulated, innate immune response with a poor adaptive response. A limited and delayed interferon I (IFN-I) and IFN-III response results in exacerbated proinflammatory cytokine production and in extensive cellular infiltrates in the respiratory tract, resulting in lung pathology

Antibodies, and the B cell and plasma cell populations responsible for their production, are key components of the human immune system’s response to SARS-CoV-2, which has caused the coronavirus disease 2019 (COVID-19) pandemic. Here, we review findings addressing the nature of antibody responses against SARS-CoV-2 and their role in protecting from infection or modulating COVID-19 disease severity.

Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified

Humanity is currently facing the challenge of two devastating pandemics caused by two very different RNA viruses: HIV-1, which has been with us for decades, and SARS-CoV-2, which has swept the world in the course of a single year. The same evolutionary strategies that drive HIV-1 evolution are at play in SARS-CoV-2. Single nucleotide mutations, multi-base insertions and deletions, recombination, and

The rapid and remarkably successful development, manufacture, and deployment of several effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is now tempered by three key challenges. First, reducing virus transmission will require prevention of asymptomatic and mild infections in addition to severe symptomatic infections. Second, the emergence of variants of concern with mutations