{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:46:25Z","timestamp":1790401585449,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI116323, AI136877, AI141325"],"award-info":[{"award-number":["AI116323, AI136877, AI141325"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nebraska Cancer and Smoking Disease Research Program","award":["LB595"],"award-info":[{"award-number":["LB595"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cryptosporidium is a genus of protozoan parasites that infect the gastrointestinal epithelium of a variety of vertebrate hosts. Intestinal epithelial cells are the first line of defense and play a critical role in orchestrating host immunity against Cryptosporidium infection. To counteract host defense response, Cryptosporidium has developed strategies of immune evasion to promote parasitic replication and survival within epithelial cells, but the underlying mechanisms are largely unclear. Using various models of intestinal cryptosporidiosis, we found that Cryptosporidium infection caused suppression of mitogen-activated protein kinase (MAPK) signaling in infected murine intestinal epithelial cells. Whereas expression levels of most genes encoding the key components of the MAPK signaling pathway were not changed in infected intestinal epithelial cells, we detected a significant downregulation of p38\/Mapk, MAP kinase-activated protein kinase 2 (Mk2), and Mk3 genes in infected host cells. Suppression of MAPK signaling was associated with an impaired intestinal epithelial defense against C. parvum infection. Our data suggest that cryptosporidial infection may suppress intestinal epithelial cell MAPK signaling associated with the evasion of host antimicrobial defense.<\/jats:p>","DOI":"10.3390\/microorganisms9010151","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T14:28:53Z","timestamp":1610461733000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cryptosporidial Infection Suppresses Intestinal Epithelial Cell MAPK Signaling Impairing Host Anti-Parasitic Defense"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-7926","authenticated-orcid":false,"given":"Wei","family":"He","sequence":"first","affiliation":[{"name":"Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"},{"name":"Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Yu","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas W.","family":"Mathy","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8380-1246","authenticated-orcid":false,"given":"Yaoyu","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-2727","authenticated-orcid":false,"given":"Lihua","family":"Xiao","sequence":"additional","affiliation":[{"name":"Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.pt.2013.03.001","article-title":"Looking for cryptosporidium: The application of advances in detection and diagnosis","volume":"5","author":"Chalmers","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1017\/S0031182014001085","article-title":"Cryptosporidium species in humans and animals: Current understanding and research needs","volume":"13","author":"Ryan","year":"2014","journal-title":"Parasitology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/503189a","article-title":"Parasitic infections: Time to tackle cryptosporidiosis","volume":"7475","author":"Striepen","year":"2013","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S1473-3099(14)70772-8","article-title":"A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium","volume":"1","author":"Checkley","year":"2015","journal-title":"Lancet Infect. 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