A balanced human diet comprises carbohydrates, fats, and proteins, along with vitamins and minerals, which are required to sustain physiological functions. In many Western diets, protein often takes c...

Direct interaction of l-arginine with NLRP3 inhibits inflammasome activation, linking metabolism to inflammation.

Intestinal CD4+ T cells migrate to the dura and brain following gut infection with bacteria or parasites, establishing a long-lived memory population capable of proliferation and cytokine production f...

Conventional laboratory mice are invaluable tools in biomedical research, but their restricted microbial complexity limits their translational relevance. H

The pulmonary epithelium maintains a thin barrier that supports efficient alveolar-capillary gas exchange while continuously encountering inhaled particulates, microbes, and toxins (1–3). This barrier favors early containment of pathogens with limited tissue damage before a broader inflammatory response develops (1–3). Within this architecture, epithelial cells sense environmental cues and release mediators that shape local immune responses (1, 4, 5). Along the airway-alveolar axis, epithelial cell identity, transcriptional state, anatomical location, and proximity to immune cells vary, generating distinct responses to the same stimulus (2). Host defense in the lung depends on coordinated signaling between epithelial cells and resident or recruited hematopoietic cells, including macrophages, monocytes, dendritic cells, neutrophils, NK cells, and T cells, which together provide antimicrobial protection (6–9).

Using CRISPR-based TCR editing, Chi et al. systematically compare gut TCRs recognizing dietary, microbial, and self-antigens to define the principles that govern peripheral Treg cell differentiation. ...

The autoimmune regulator (Aire) promotes T cell tolerance through promiscuous gene expression in medullary thymic epithelial cells, but growing evidence suggests that it has functions beyond its canon...

IL-1 family signalling drives host mucosal defence against Candida albicans and, together with neutrophils, prevents mucosal–systemic dissemination and life-threatening fungal disease.

TRAM is a regulator of myddosome assembly through dissociating MyD88 from the TLR–TIRAP complex to enable myddosome maturation and durable downstream signal transduction.

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

Pathogenic bacteria release ATP that is sensed by airway tuft cells. In response, tuft cells produce leukotrienes that orchestrate early antibacterial immunity by promoting neutrophil recruitment and ...

Diaz-Olea et al. identify indoles as tryptophan breakdown products that induce anti-tumor immunity and inhibit melanoma growth. Indoles, produced upon tryptophan breakdown by Bacteroides uniformis- (h...

Tang et al. reveal that dietary pectin drives Bacteroides uniformis surface remodeling to enrich the surface glycosphingolipid HexCer. Neutrophils sense this signal via CLEC4E to promote IgA productio...

This study provides evidence for a key role of TNFR1, as expressed by malignant cells, in orchestrating a pro-tumor immunosuppressive environment through s

Liu et al. show that soy fiber enhances colonization resistance against Salmonella Enteritidis by enriching Akkermansia and its metabolite harmaline. Harmaline suppresses bacterial virulence and limit...

A signal that can help breast cancer cells grow may also increase immune responses and boost immune therapy.

Martini, Hofmann, et al. identify C. albicans-specific Th17 cells targeting fungal EV proteins that predominantly reside in the human oral mucosa at homeostasis. However, these oral-residing cells exhibit TCR overlap with gut Th17 cells. During intestinal inflammation, C. albicans-specific Th17 cells retain their antigen specificity but acquire pathogenic traits, highlighting how oral immunity impacts intestinal disease.

Granucci and colleagues identify microbial adhesion to myeloid cells as a critical initiating event that precedes engagement of pattern recognition receptors.

Neutrophil extracellular traps (NETs) feature a branched chromatin architecture whose origin and function remain unknown. We found that NET branching is mediated by RAD51, a protein generating DNA jun...

Mechanisms governing T cell responses to food or microbes have been characterized; however, whether they also regulate gut autoimmunity is unknown. Zhou et al. uncover that self-antigens depend on distinct subsets of antigen-presenting cells compared with dietary antigens for tolerogenic and effector T cell responses. This translates into antigen-source dependent disease susceptibility.

The complement system is an evolutionarily conserved arm of innate immunity, which forms one of the first lines of host response to pathogens and assists in the clearance of debris. A deficiency in ke...