{"id":6383,"date":"2022-09-29T17:41:26","date_gmt":"2022-09-29T21:41:26","guid":{"rendered":"https:\/\/med.virginia.edu\/pathology\/2022\/09\/29\/md-jashim-uddin-phd-2021\/"},"modified":"2025-05-16T21:13:51","modified_gmt":"2025-05-17T01:13:51","slug":"md-jashim-uddin-phd-2021","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/pathology\/2022\/09\/29\/md-jashim-uddin-phd-2021\/","title":{"rendered":"Md Jashim Uddin, PhD, 2021"},"content":{"rendered":"

Type 2 immunity and amebiasis<\/h1>\n

Advisor:<\/span><\/strong><\/h4>\n

Petri, William, Medicine, Microbiology, Immunology and Cancer Biology, and Pathology, University of Virginia<\/p>\n

Abstract:<\/span><\/strong><\/h4>\n
\n

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, an infection that manifests as colitis, and in some cases, liver abscess. It is also one of the primary causative agents of severe childhood diarrhea in regions with poor sanitation and hygiene. E. histolytica enters the host gut through fecally contaminated food and water, infects intestinal epithelial cells, and causes tissue injury and cellular death. A better understanding of host protective factors is key to developing an effective remedy. Therefore, we characterized the host innate immune response to amebic infection.<\/p>\n

Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage during infection. IL-33 is implicated in protection from tissue damage and clearance of infection during bacterial, helminthic, and fungal infections. We discovered that treatment with recombinant IL-33 protected mice from amebic infection and intestinal tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to infection and weight loss. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the cecum. IL-33-mediated protection was accompanied by increased expression in the cecum of IL-5, IL-13, goblet cells, eosinophils, and M2 macrophages (CD206+), emphasizing the role of a type 2 immune response in IL-33 mediated protection. Interestingly, administration of IL-33 protected RAG2-\/- mice but not RAG2-\/-\u03b3c-\/- mice, demonstrating that IL-33 mediated protection occurred in the absence of T or B cells but required the presence of innate lymphoid cells (ILCs). Moreover, IL-33-conferred upregulation of type 2 cytokines was lost in RAG2-\/-\u03b3c-\/- but not in RAG2-\/- mice. IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in the cecum of RAG2-\/- mice. Adoptive transfer of ILC2s to RAG2-\/-\u03b3c-\/- mice restored IL-33 mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.<\/p>\n

We also characterized type 2 immunity between amebic-resistant C57BL\/6J mice and amebic-susceptible CBA\/J mice. At baseline and after amebic infection, there was a significantly higher IL13+ILC2s in C57BL\/6J mice compared to CBA\/J mice. In addition, a downstream effector protein of ILC2 signaling, Chil3, was significantly higher in C57BL\/6J mice than CBA\/J mice. Moreover, supplementing CBA\/J mice with exogenous Chil3 assisted in faster clearance of amebic trophozoites. Finally, we observed that fecal microbiota transplantation between C57BL\/6J and CBA\/J mice transferred susceptibility\/resistance to amebiasis.<\/p>\n

Altogether, we identified that the IL-33-ILC2 pathway protects from amebic colitis. Our data also demonstrate that the microbiota-ILC2 interaction might play a role in conferring resistance to amebiasis.<\/p>\n<\/div>\n

Full Dissertation:<\/strong><\/h4>\n

https:\/\/doi.org\/10.18130\/4nzs-rr36<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Type 2 immunity and amebiasis Advisor: Petri, William, Medicine, Microbiology, Immunology and Cancer Biology, and Pathology, University of Virginia Abstract: The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, an infection that manifests as colitis, and in some cases, liver abscess. It is also one of the primary causative agents of severe childhood […]<\/p>\n","protected":false},"author":1184,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[41],"tags":[],"class_list":["post-6383","post","type-post","status-publish","format-standard","hentry","category-phd-defenses"],"acf":false,"yoast_head":"\nMd Jashim Uddin, PhD, 2021 - Department of Pathology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/pathology\/2022\/09\/29\/md-jashim-uddin-phd-2021\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Md Jashim Uddin, PhD, 2021 - Department of Pathology\" \/>\n<meta property=\"og:description\" content=\"Type 2 immunity and amebiasis Advisor: Petri, William, Medicine, Microbiology, Immunology and Cancer Biology, and Pathology, University of Virginia Abstract: The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, an infection that manifests as colitis, and in some cases, liver abscess. 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