Itaconate as a potential target for antimalarial therapy.

In a recent publication, Ramalho et al. investigated monocyte-derived dendritic cell (MODC) mobilization in response to Plasmodium infection. The authors showed that elevated levels of itaconate in MODCs results in reduced CD8 T cell activation and that the absence of itaconate is associated with enhanced parasite control.

T helper 1 effector memory CD4+ T cells protect the skin from poxvirus infection.

Poxvirus infections of the skin are a recent emerging public health concern, yet the mechanisms that mediate protective immunity against these viral infections remain largely unknown. Here, we show that T helper 1 (Th1) memory CD4+ T cells are necessary and sufficient to provide complete and broad protection against poxvirus skin infections, whereas memory CD8+ T cells are dispensable. Core 2 O-glycan-synthesizing Th1 effector memory CD4+ T cells rapidly infiltrate the poxvirus-infected skin microenvironment and produce interferon γ (IFNγ) in an antigen-dependent manner, causing global changes in gene expression to promote anti-viral immunity. Keratinocytes express IFN-stimulated genes, upregulate both major histocompatibility complex (MHC) class I and MHC class II antigen presentation in an IFNγ-dependent manner, and require IFNγ receptor (IFNγR) signaling and MHC class II expression for memory CD4+ T cells to protect the skin from poxvirus infection. Thus, Th1 effector memory CD4+ T cells exhibit potent anti-viral activity within the skin, and keratinocytes are the key targets of IFNγ necessary for preventing poxvirus infection of the epidermis.

Molecular evolution of DNMT1 in vertebrates: Duplications in marsupials followed by positive selection.

DNA methylation is mediated by a conserved family of DNA methyltransferases (Dnmts). The human genome encodes three active Dnmts (Dnmt1, Dnmt3a and Dnmt3b), the tRNA methyltransferase Dnmt2, and the regulatory protein Dnmt3L. Despite their high degree of conservation among different species, genes encoding Dnmts have been duplicated and/or lost in multiple lineages throughout evolution, indicating that the DNA methylation machinery has some potential to undergo evolutionary change. However, little is known about the extent to which this machinery, or the methylome, varies among vertebrates. Here, we study the molecular evolution of Dnmt1, the enzyme responsible for maintenance of DNA methylation patterns after replication, in 79 vertebrate species. Our analyses show that all studied species exhibit a single copy of the DNMT1 gene, with the exception of tilapia and marsupials (tammar wallaby, koala, Tasmanian devil and opossum), each of which displays two apparently functional DNMT1 copies. Our phylogenetic analyses indicate that DNMT1 duplicated before the radiation of major marsupial groups (i.e., at least ~75 million years ago), thus giving rise to two DNMT1 copies in marsupials (copy 1 and copy 2). In the opossum lineage, copy 2 was lost, and copy 1 recently duplicated again, generating three DNMT1 copies: two putatively functional genes (copy 1a and 1b) and one pseudogene (copy 1ψ). Both marsupial copies (DNMT1 copies 1 and 2) are under purifying selection, and copy 2 exhibits elevated rates of evolution and signatures of positive selection, suggesting a scenario of neofunctionalization. This gene duplication might have resulted in modifications in marsupial methylomes and their dynamics.