Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern.

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants.

Uptake of Plasmodium chabaudi hemozoin drives Kupffer cell death and fuels superinfections.

Kupffer cells (KCs) are self-maintained tissue-resident macrophages that line liver sinusoids and play an important role on host defense. It has been demonstrated that upon infection or intense liver inflammation, KCs might be severely depleted and replaced by immature monocytic cells; however, the mechanisms of cell death and the alterations on liver immunity against infections deserves further investigation. We explored the impact of acute Plasmodium infection on KC biology and on the hepatic immune response against secondary infections.

Gluconeogenesis: Adding a new piece to the puzzle of malaria parasitism.

Disorders of carbohydrate metabolism, including hypoglycemia and lactic acidosis, are common features of malaria. In this issue of Cell Metabolism, Ramos et al. report that regulation of gluconeogenesis and glycemia by the host glucose-6-phosphatase catalytic subunit 1 (G6Pc1) is a key metabolic step that affects both Plasmodium replication and clinical outcome of disease.

Periodic Parasites and Daily Host Rhythms.

Biological rhythms appear to be an elegant solution to the challenge of coordinating activities with the consequences of the Earth's daily and seasonal rotation. The genes and molecular mechanisms underpinning circadian clocks in multicellular organisms are well understood. In contrast, the regulatory mechanisms and fitness consequences of biological rhythms exhibited by parasites remain mysterious.

Monocyte-derived dendritic cells in malaria.

The pathogenesis of malaria is a multifactorial syndrome associated with a deleterious inflammatory response that is responsible for many of the clinical manifestations. While dendritic cells (DCs) play a critical role in initiating acquired immunity and host resistance to infection, they also play a pathogenic role in inflammatory diseases. In our recent studies, we found in different rodent malaria models that the monocyte-derived DCs (MO-DCs) become, transiently, a main DC population in spleens and inflamed non-lymphoid organs.

Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.

The Plasmodium cell cycle, wherein millions of parasites differentiate and proliferate, occurs in synchrony with the vertebrate host's circadian cycle. The underlying mechanisms are unknown. Here we addressed this question in a mouse model of Plasmodium chabaudi infection.

Splenic differentiation and emergence of CCR5CXCL9CXCL10 monocyte-derived dendritic cells in the brain during cerebral malaria.

Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11bF4/80CD11cMHCIIDC-SIGNLy6c and express high levels of CCR5, CXCL9 and CXCL10 (CCR5CXCL9/10 MO-DCs).

DNA-Containing Immunocomplexes Promote Inflammasome Assembly and Release of Pyrogenic Cytokines by CD14+ CD16+ CD64high CD32low Inflammatory Monocytes from Malaria Patients.

Unlabelled: High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-κB transcriptional signature.