Maria Cecilia Campos Canesso, Ph.D.

The highly specialized intestinal immune system faces the challenge of tolerating foreign nutrients and the symbiotic microbiome, while providing protective immunity against pathogens. Antigen-presenting cells (APCs) are key players in orchestrating intestinal homeostasis, finely tuning different immune responses by presenting luminal antigens and inducing functional differentiation of CD4+ T cells into regulatory or pro-inflammatory subsets. Dysregulation of this critical balance can lead to severe disease such as food allergy and inflammatory bowel diseases (IBD) both of which lack efficient therapies. Attempts to design such treatments will benefit from a deeper understanding of the nature of immune cell communication that dictates tolerance or inflammation to food and microbes, a decades-long technical challenge in the field. Furthermore, immunological events that take place in early life have profound and long-lasting impact in adulthood susceptibility to disease. The neonatal intestine is a unique environment primed for establishing immune tolerance to microbiota and dietary antigens, however we still lack detailed understanding of the cellular and molecular basis for this phenomenon. It therefore offers the opportunity to uncover exciting biology during this important window of opportunity to prevent diseases before their onset.

Despite its importance, the spatial and temporal organization of APC-T cell interactions that guide intestinal immune outcomes remains poorly understood. We recently discovered that there is a division of labor between different APC subsets in the presentation of dietary and pathogen-derived antigens, likely as a mechanism to prevent food-specific Th2 responses even amid strong type 2 immunity driven by helminth infection. We hypothesize that APCs specialized for different functions exist in the intestine and that continuous dynamic reprogramming of APCs subsets by luminal content dictate tolerance or immunity to food and microbes. Leveraging powerful new tools that we developed the application to study cell-cell interactions in the intestine, we aim to define the principles of immune education in the gut across three biologically connected contexts: colonization by commensals, dietary antigen exposure, and maternal transmission of antigens via breastmilk. Together, these studies will reveal how distinct APC programs shape the fate of T and B cells across development, and how their misregulation leads to disease, enabling both the rational design of targeted immunotherapies and opening the door to new line of investigation at the intersection of cellular communication, mucosal immunology and developmental biology.

1. Canesso MCC^, de Castro TBR, Nakandakari-H S, Lockhart A, Luehr J, Bortolatto J, Parsa R, Esterházy D, Lyu M, Liu TT, Murphy KM, Sonnenberg GF, Reis BS, Victora GD^, Mucida D^. Identification of antigen-presenting cell-T cell interactions driving immune responses to food. Science. 2025 Mar. PubMed PMID: 39700315; PMCID: PMC12017586. (^Corresponding author). https://www.science.org/doi/10.1126/science.ado5088
2. Nakandakari-H S, Walker S*, Canesso MCC*, van der Heide V, Chudnovskiy A, Kim DY, Jacobsen JT, Parsa R, Bilanovic J, Parigi SM, Fiedorczuk K, Fuchs E, Bilate AM, Pasqual G, Mucida D, Kamphorst AO,  Pritykin Y, Victora GD. Universal recording of immune cell interactions in vivo. Nature, 2024 Mar 6. PubMed PMID 38448581 PMCID 11078586. (*These authors contributed equally). https://www.nature.com/articles/s41586-024-07134-4
3. Lockhart A, Reed A, Castro TBR, Herman C, Canesso MCC, Mucida D. Dietary protein shapes the profile and repertoire of intestinal CD4+ T cells. J Exp Med, 2023 Aug 7. PubMed PMID 37191720 PMCID 10192604. https://rupress.org/jem/article/220/8/e20221816/214115/Dietary-protein-shapes-the-profile-and-repertoire
4. Canesso MCC, Cassini-Vieira P, Moreira CF, Luong S, Rachid MA Martins FS, Teixeira MM, Vieira AT, Mackay CR, Barcelos LS. Dietary fiber improves skin wound healing and scar formation through the metabolite-sensing receptor GPR43. J Invest Dermatol, 2023 Mar 23. PubMed PMID 36965576. https://www.sciencedirect.com/science/article/pii/S0022202X23019395?via%3Dihub
5. Nakandakari-H S, Parsa R, Reis BS, Carvalho RVH, Mesin L, Hoffmann HH, Bortolatto J, Maramatsu H, Lin PJC, Bilate AM, Rice C, Pardi N, Mucida D, Victora GD, Canesso MCC^. A minimally-edited mouse model for infection with multiple SARS-CoV-2 strains. Front Immunol. 2022 Nov14. PubMed PMID 36451809, PMC9703079. (^Corresponding author). https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1007080/full Canesso MCC^, Moreira TG^, Faria AMC^. Compartmentalization of gut immune responses: mucosal niches and lymph node peculiarities. Immunol Lett. 2022 Oct. PubMed PMID 36309158. (^Corresponding author). https://www.sciencedirect.com/science/article/pii/S0165247822001468?via%3Dihub
6. Esterhazy D*, Canesso MCC*, Mesin L, Muller PA, Castro TBR, Lockhart A, ElJalbay M, Faria AMC, Mucida D. Compartmentalized gut lymph node drainage dictates adaptive immune responses. Nature. 2019 May. PubMed PMID 30988509; PMC 6587593. (*These authors contributed equally). https://www.nature.com/articles/s41586-019-1125-3
7. Canesso MCC, Lemos L, Neves TC, Marim FM, Castro TBR, Veloso ÉS, Queiroz CP, Ahn J, Santiago HC, Cara DC, Silva JA, Martins FS, Ferreira E, Vieira AT, Barber GN, Oliveira SC, Faria AMC. The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation. Mucosal Immunol. 2017 Dec20; PubMed PMID:29346345. https://www.sciencedirect.com/science/article/pii/S1933021922005554?via%3Dihub
8. Canesso MCC, Vieira AT, Castro TBR, Schirmer BGA, Cisalpino D, Martins FS, Rachid MA, Nicoli JR, Teixeira MM, Barcelos LS. Skin Wound Healing Is Accelerated and Scarless in the Absence of Commensal Microbiota. J Immunol. 2014 Nov 15;193(10):5171-80. PubMed PMID:25326026. https://academic.oup.com/jimmunol/article/193/10/5171/7960509?login=true#google_vignette