Biology subjects

Merolle, M.

Publications and source records attributed to Merolle, M..

3 recordsLinked to original sources

bioRxiv2026

The role of integrins in T cell-mediated resistance to Cryptosporidium parvum

Cryptosporidium is a protozoan that infects epithelial cells of the small intestine and is a cause of diarrhea and death in immunocompromised individuals and malnourished children. Immunity to this parasite is mediated by an intestinal T cell response, which is generated in gut-associated lymphoid tissues and dependent on type 1 conventional dendritic cells (cDC1s). The initial priming of T cells is accompanied by changes in integrin expression and subsequent trafficking to the site of infection. The role of specific integrins in trafficking to the ileum during cryptosporidiosis is largely unknown. The development of a transgenic Cryptosporidium strain that expresses MHCI and MHCII-restricted model antigens provides the ability to track T cell responses to this parasite. Our studies in this system revealed marked changes in the integrin profile of parasite-specific T cells as they are activated and traffic to the gut, and demonstrate that cDC1s contribute to the expression of the integrins 4, {beta}7, {beta}1, and L. Surprisingly, blockade of the canonical gut-homing integrin 4{beta}7 does not impact the ability of parasite-specific T cells to access the gut. However, blockade of integrin L decreases the parasite-specific T cell frequency at the site of infection and delays control of parasite burden. These datasets highlight an 4{beta}7-independent mechanism of T cell trafficking to the small intestine and indicate that L is an integrin required for T cell-mediated resistance to Cryptosporidium.

immunology↗

bioRxiv2026

Improving peptide vaccine manufacturability without sacrificing immunogenicity: substitution of methionine and cysteine with oxidation-resistant isosteres

AO_SCPLOWBSTRACTC_SCPLOWVaccines comprising peptide antigens for inducing T cell immunity are being developed for a broad range of therapeutic applications including prevention and treatment of cancer, autoimmunity, and infectious diseases. However, many peptide antigens contain cysteine and/or methionine, which are prone to form oxidation products that can present challenges to manufacturing and reduce biological activity. To address this challenge, we introduced oxidation resistant (OXR) antigens wherein the cysteine and methionine residues of naturally occurring, wild type (WT) peptide antigens are substituted with isosteric residues that are structurally related but omit the oxidation-prone sulfur atom. Our results showed that vaccination with OXR antigens substituting cysteine and methionine with isosteres alpha-aminobutyric acid and norleucine, respectively, induced immune responses to the WT antigen that were equivalent or higher than those induced by vaccination with WT antigens. T cell responses were not affected by the position of the amino acid substitutions indicating that the isosteres do not negatively impact major histocompatibility complex (MHC) binding or T cell recognition. The T cells induced were high quality and associated with anti-tumor efficacy in vivo. Interestingly, substitution of cysteine with serine, which replaces the sulfur for an oxygen, did not yield cross-reactive T cell responses, highlighting the high degree of molecular discernment of peptide-MHC processing and presentation. In sum, OXR antigens provide a generalizable strategy for eliminating sulfur oxidation products and improving the manufacturability and shelf-life of peptide-based vaccines without affecting desired biologic activity.

immunology↗

bioRxiv2025

Diverse infections transcriptionally reprogram the intestinal epithelium and epithelial-immune cell interactions

The distal small intestine plays vital roles in host physiology by regulating nutrient and fluid homeostasis. Despite being impacted in Crohns disease and a major target for a range of infections, we know relatively little about the complexity of cellular responses and cell-cell communication in the ileum during infection. Single cell and spatial transcriptomics have emerged as powerful technologies to study tissue heterogeneity in the gut, but these tools have focused on the large intestine, in part due to the accessibility of this tissue for biopsies and its importance in cancer. Here we present GutPath, an atlas of over 500,000 single cells with RNA and protein expression profiles for 91 cell states in the ileum across diverse infectious archetypes. We show that GutPath accurately captures established immune responses to infection while revealing pathogen-specific responses in enterocytes. To highlight the discovery potential of this atlas, we identify a novel enterocyte cell state present during Yersinia pseudotuberculosis infection that is spatially linked to bacterial load and tissue pathology. GutPath establishes a much-needed resource for the immunology community that will accelerate the study of the transcriptional diversity of cellular landscapes in the small intestine.

immunology↗