Innate immune cells that are epigenetically reprogrammed by infection can modify host responses to subsequent infections. Lercher et al. have identified epigenetic reprogramming of murine airway-resident macrophages following recovery from SARS-CoV-2 infection, conferring protection from pathology and lethality following secondary influenza A virus (IAV) challenge without reducing viral titers.

A recent study by Ascic et al. demonstrates that in situ reprogramming of tumor cells into conventional dendritic cell (cDC)-like cells using viral-PIB transcription factors creates an immunogenic tumor microenvironment with T cell recruitment and activation. The study highlights the potential of tumor-specific cancer immunotherapy using in vivo reprogrammed cDCs.

Combinations of the highly polymorphic KIR and HLA-I genes are associated with numerous human diseases. Interpreting these associations requires a molecular understanding of the multiple killer-cell immunoglobulin-like receptor (KIR)–human leukocyte antigen-1 (HLA-I) receptor–ligand interactions on natural killer (NK) cells and identifying the salient features that underlie disease risk. We hypothesize that a critical discriminating factor in KIR–HLA-I interactions is the selective detection of HLA-I-bound peptides by KIRs. We propose a ‘peptide selectivity model’, where high-avidity KIR–HLA-I interactions reflect low selectivity for peptides conferring consistent NK cell inhibition across different tissue immunopeptidomes. Conversely, lower-avidity interactions (including those with activating KIRs) are more dependent on HLA-I-bound peptide sequence, requiring an appreciation of how HLA-I immunopeptidomes influence KIR binding and regulate NK cell function. Relevant to understanding N

The recent discovery by Lu and colleagues of Tomasiella immunophila, a bacterium that degrades IgA, offers insights into microbial influences on mucosal immunity and evolutionary immune trade-offs. By modulating IgA titers, T. immunophila influences the dynamic interactions and balance between the host and pathogen. This has implications for immune health, microbiome research, and therapeutics.

A recent study by Ascic et al. demonstrates that in situ reprogramming of tumor cells into conventional dendritic cell (cDC)-like cells using viral-PIB transcription factors creates an immunogenic tumor microenvironment with T cell recruitment and activation. The study highlights the potential of tumor-specific cancer immunotherapy using in vivo reprogrammed cDCs.

Following on from the discovery that innate immune pathways are shared widely across the tree of life comes another surprise: Hobbs et al. show that viruses targeting animals and bacteria also use highly conserved tools to fight back. Why such mechanisms remain seemingly unchanged despite the rapid coevolution among hosts and pathogens is now a key open question for the field.