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Previously described host\u2010directed therapies using toll\u2010like receptor (TLR) activation\u2010based strategies have proven effective in controlling neonatal diseases, including cryptosporidiosis. In this study, we investigated the effect of nucleotide\u2010binding oligomerization domain (NOD) receptors stimulation on the control of enteric infection by the protozoan\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    in neonatal mice. NOD2 stimulation by intraperitoneal injection of muramyl dipeptide (MDP) resulted in a rapid reduction in the parasite burden. The protective effect was associated with increased pro\u2010inflammatory cytokine and antimicrobial peptide gene expression and a rapid influx of neutrophils to the site of infection, whereas NOD1 stimulation did not show a protective effect. The protective mechanism did not involve microbiota participation but involved IFN\u2010\u03b3 and IL\u201022 cytokines and was associated with increased intestinal epithelium renewal in infected neonates. Our findings showed that stimulating neonatal mice with the bacterial ligand MDP, which targets the NOD2 receptor, actively contributes to the nonspecific clearance of\n                    <jats:italic>C. parvum<\/jats:italic>\n                    infection by eliminating or renewing infected epithelial cells.\n                  <\/jats:p>","DOI":"10.1002\/eji.70080","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:31:10Z","timestamp":1761021070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Administration of the NOD2 Agonist MDP Reduces\n                    <i>Cryptosporidium parvum<\/i>\n                    Infection in Neonatal Mice Through IL\u201022 Involvement"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3788-9539","authenticated-orcid":false,"given":"M\u00e9gane","family":"Fernandez","sequence":"first","affiliation":[{"name":"INRAE, Universit\u00e9 de Tours, UMR 1282 Infectiologie et Sant\u00e9 Publique, Laboratoire AIM  Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Pezier","sequence":"additional","affiliation":[{"name":"INRAE, Universit\u00e9 de Tours, UMR 1282 Infectiologie et Sant\u00e9 Publique, Laboratoire AIM  Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Pichon","sequence":"additional","affiliation":[{"name":"INRAE, Universit\u00e9 de Tours, UMR 1282 Infectiologie et Sant\u00e9 Publique, Laboratoire IMI  Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves Le","family":"Vern","sequence":"additional","affiliation":[{"name":"INRAE, 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