Immunology of Cryptosporidiosis
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
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Immunology of Cryptosporidiosis Guoku Hu, Yaoyu Feng, Steven P. O’Hara, and Xian-Ming Chen
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., Tolllike 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.
G. Hu • X.-M. Chen (*) Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA e-mail: [email protected]; [email protected] Y. Feng School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China e-mail: [email protected] S.P. O’Hara Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA e-mail: [email protected] S.M. Caccio` and G. Widmer (eds.), Cryptosporidium: parasite and disease, DOI 10.1007/978-3-7091-1562-6_10, © Springer-Verlag Wien 2014
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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.
10.1
Introduction
Host immune defense is critical to eliminate Cryptosporidium spp. infection. The self-limiting nature of Cryptosporidium infection in immunocompetent subjects suggests that the host activates an efficient immune response to eliminate the infection. After entry into host epithelial cells, the parasite resides within a unique intracellular but extracytoplasmic niche, separating the parasite from a direct interaction with other cell types. Therefore, Cryptosporidium spp. are classified as “minimally invasive” mucosal pathogens (Chen et al. 2002).
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