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Immunology of Cryptosporidiosis

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Cryptosporidium: parasite and disease

Abstract

Cryptosporidium spp. infect the gastrointestinal epithelium of vertebrate hosts. Intestinal species typically cause self-limiting diarrhea in immunocompetent individuals, suggesting an efficient host immune defense to eliminate the infection. Both innate and adaptive immunity are involved in host anti-parasite defense. Because of the “minimally invasive” nature of Cryptosporidium infection, mucosal epithelial cells are critical to the host’s anti-Cryptosporidium immunity. Epithelial cells not only provide the first and rapid defense against Cryptosporidium infection, but also mobilize immune effector cells to the infection site to activate adaptive immunity. Attachment to the apical cell surface by Cryptosporidium, as well as molecules inserted into host cells after attachment, can activate host cell signal pathways and thereby alter cell function. Pathogen recognition receptors (e.g., Toll-like receptors) in epithelial cells recognize Cryptosporidium and initiate downstream signaling pathways (e.g., NF-kappaB) which trigger a series of antimicrobial responses and activate adaptive immunity. Non-coding RNAs are critical regulators of mucosal immunity to infection, while release of exosomes from epithelial cells may be a relatively unexplored, important component of mucosal anti-parasite defense. Conversely, it appears that Cryptosporidium has also developed strategies of immune evasion to escape host immunity, at least at the early stage of infection. Immune responses contribute to the pathophysiologic features of cryptosporidiosis. A better understanding the immunology of cryptosporidiosis will provide a framework for the potential development of novel therapeutic strategies.

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Acknowledgments

The authors thank the members of the Chen lab, particularly Rui Zhou, Ai-Yu Gong, Jun Liu, Dongqing Chen, Grace Yang and Alex N. Eischeid for their contributions towards understanding Cryptosporidium-epithelial cell interactions. Support from the National Institutes of Health (AI071321 and AI095532) and the Nebraska Biomedical Research Program (LB692) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, 68178, USA

    Guoku Hu & Xian-Ming Chen

  2. School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, China

    Yaoyu Feng

  3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Steven P. O’Hara

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  1. Guoku Hu
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  4. Xian-Ming Chen
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Correspondence to Xian-Ming Chen .

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  1. Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy

    Simone M. Cacciò

  2. Tufts Cummings School of Veterinary Medicine Division of Infectious Diseases, North Grafton, Massachusetts, USA

    Giovanni Widmer

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Hu, G., Feng, Y., O’Hara, S.P., Chen, XM. (2014). Immunology of Cryptosporidiosis. In: Cacciò, S., Widmer, G. (eds) Cryptosporidium: parasite and disease. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1562-6_10

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