Hostname: page-component-8448b6f56d-jr42d Total loading time: 0 Render date: 2024-04-23T20:49:27.047Z Has data issue: false hasContentIssue false
  • English
  • Français

Non-coding RNAs in epithelial immunity to Cryptosporidium infection

Published online by Cambridge University Press:  14 May 2014

RUI ZHOU ,
YAOYU FENG  and
XIAN-MING CHEN
RUI ZHOU*
Affiliation:
School of Basic Medical Sciences, Wuhan University, Hubei 430071, China
YAOYU FENG
Affiliation:
School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
XIAN-MING CHEN*
Affiliation:
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA
*
*Corresponding authors: School of Basic Medical Sciences, Wuhan University, 185 Donghu Road, Hubei 430071, China. E-mail: ruizhou@whu.edu.cn; and Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. E-mail: xianmingchen@creighton.edu
*Corresponding authors: School of Basic Medical Sciences, Wuhan University, 185 Donghu Road, Hubei 430071, China. E-mail: ruizhou@whu.edu.cn; and Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. E-mail: xianmingchen@creighton.edu
Get access Rights & Permissions [Opens in a new window]

Summary

Cryptosporidium spp. is a protozoan parasite that infects the gastrointestinal epithelium and causes diarrhoeal disease worldwide. It is one of the most common pathogens responsible for moderate to severe diarrhoea in children younger than 2 years. Because of the ‘minimally invasive’ nature of Cryptosporidium infection, mucosal epithelial cells are critical to the host's anti-Cryptosporidium immunity. Gastrointestinal epithelial cells not only provide the first and most rapid defence against Cryptosporidium infection, they also mobilize immune effector cells to the infection site to activate adaptive immunity. Recent advances in genomic research have revealed the existence of a large number of non-protein-coding RNA transcripts, so called non-coding RNAs (ncRNAs), in mammalian cells. Some ncRNAs may be key regulators for diverse biological functions, including innate immune responses. Specifically, ncRNAs may modulate epithelial immune responses at every step of the innate immune network following Cryptosporidium infection, including production of antimicrobial molecules, expression of cytokines/chemokines, release of epithelial cell-derived exosomes, and feedback regulation of immune homoeostasis. This review briefly summarizes the current science on ncRNA regulation of innate immunity to Cryptosporidium, with a focus on microRNA-associated epithelial immune responses.

Keywords

CryptosporidiumncRNAsmiRNAslincRNAsepithelial cellsimmunity
Type
Review Article
Information
Parasitology , Volume 141 , Issue 10 , September 2014 , pp. 1233 - 1243
Check for updates
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abrahamsen, M. S., Templeton, T. J., Enomoto, S., Abrahante, J. E., Zhu, G., Lancto, C. A., Deng, M., Liu, C., Widmer, G., Tzipori, S., Buck, G. A., Xu, P., Bankier, A. T., Dear, P. H., Konfortov, B. A., Spriggs, H. F., Iyer, L., Anantharaman, V., Aravind, L. and Kapur, V. (2004). Complete genome sequence of the apicomplexan. Cryptosporidium parvum . Science 304, 441–445. doi: 10.1126/science.1094786.Google Scholar
Asirvatham, A. J., Gregorie, C. J., Hu, Z., Magner, W. J. and Tomasi, T. B. (2008). MicroRNA targets in immune genes and the Dicer/Argonaute and ARE machinery components. Molecular Immunology 45, 1995–2006. doi: 10.1016/j.molimm.2007.10.035.Google Scholar
Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297. doi: 10.1016/S0092-8674(04)00045-5.Google Scholar
Bhatnagar, S. and Schorey, J. S. (2007). Exosomes released from infected macrophages contain Mycobacterium avium glycopeptidolipids and are proinflammatory. Journal of Biological Chemistry 282, 25779–25789. doi: 10.1074/jbc.M702277200.Google Scholar
Blikslager, A. T., Moeser, A. J., Gookin, J. L., Jones, S. L. and Odle, J. (2007). Restoration of barrier function in injured intestinal mucosa. Physiological Reviews 87, 545–564. doi: 10.1152/physrev.00012.2006.Google Scholar
Borad, A. and Ward, H. (2010). Human immune responses in cryptosporidiosis. Future Microbiology 5, 507–519. doi: 10.2217/fmb.09.128.Google Scholar
Carpenter, S., Aiello, D., Atianand, M. K., Ricci, E. P., Gandhi, P., Hall, L. L., Byron, M., Monks, B., Henry-Bezy, M., Lawrence, J. B., O'Neill, L. A., Moore, M. J., Caffrey, D. R. and Fitzgerald, K. A. (2013). A long noncoding RNA mediates both activation and repression of immune response genes. Science 341, 789–792. doi: 10.1126/science.1240925.Google Scholar
Chakravorty, S. J., Cockwell, P., Girdlestone, J., Brooks, C. J. and Savage, C. O. (2002). Fractalkine expression on human renal tubular epithelial cells: potential role in mononuclear cell adhesion. Clinical and Experimental Immunology 129, 150–159. doi: 10.1046/j.1365-2249.2002.01906-x.Google Scholar
Chaumeil, J., Le Baccon, P., Wutz, A. and Heard, E. (2006). A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes and Development 20, 2223–2237. doi: 10.1101/gad.380906.Google Scholar
Chen, X. M., Keithly, J. S., Paya, C. V. and LaRusso, N. F. (2002). Cryptosporidiosis. New England Journal of Medicine 346, 1723–1731. doi: 10.1056/NEJMra013170.Google Scholar
Chen, X. M., O'Hara, S. P., Nelson, J. B., Splinter, P. L., Small, A. J., Tietz, P. S., Limper, A. H. and LaRusso, N. F. (2005). Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-kappaB. Journal of Immunology 175, 7447–7456.Google Scholar
Chen, X. M., Splinter, P. L., O'Hara, S. P. and LaRusso, N. F. (2007). A cellular micro-RNA, let-7i, regulates toll-like receptor 4 expression and contributes to cholangiocyte immune responses against Cryptosporidium parvum infection. Journal of Biological Chemistry 282, 28929–28938. doi: 10.1074/jbc.M702633200.Google Scholar
Choi, S. M., McAleer, J. P., Zheng, M., Pociask, D. A., Kaplan, M. H., Qin, S., Reinhart, T. A. and Kolls, J. K. (2013). Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is required for host defense against MRSA pneumonia. Journal of Experimental Medicine 210, 551–561. doi: 10.1084/jem.20120260.Google Scholar
Dommett, R., Zilbauer, M., George, J. T. and Bajaj-Elliott, M. (2005). Innate immune defence in the human gastrointestinal tract. Molecular Immunology 42, 903–912. doi: 10.1016/j.molimm.2004.12.004.Google Scholar
Dong, H. and Chen, X. (2006). Immunoregulatory role of B7-H1 in chronicity of inflammatory responses. Cellular and Molecular Immunology 3, 179–187.Google Scholar
Gong, A. Y., Zhou, R., Hu, G., Liu, J., Sosnowska, D., Drescher, K. M., Dong, H. and Chen, X. M. (2010). Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513. Journal of Infectious Diseases 201, 160–169. doi: 10.1086/648589.Google Scholar
Gong, A. Y., Hu, G., Zhou, R., Liu, J., Feng, Y., Soukup, G. A. and Chen, X. M. (2011). MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection. International Journal for Parasitology 41, 397–403. doi: 10.1016/j.ijpara.2010.11.011.CrossRefGoogle ScholarPubMed
Goodgame, R. W. (1996). Understanding intestinal spore-forming protozoa: cryptosporidia, microsporidia, isospora, and cyclospora. Annals of Internal Medicine 124, 429–441. doi: 10.7326/0003-4819-124-4-199602150-00008.CrossRefGoogle ScholarPubMed
Gookin, J. L., Chiang, S., Allen, J., Armstrong, M. U., Stauffer, S. H., Finnegan, C. and Murtaugh, M. P. (2006). NF-kappaB-mediated expression of iNOS promotes epithelial defense against infection by Cryptosporidium parvum in neonatal piglets. American Journal of Physiology – Gastrointestinal and Liver Physiology 290, G164–G174. doi: 10.1152/ajpgi.00460.2004.Google Scholar
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., Cabili, M. N., Jaenisch, R., Mikkelsen, T. S., Jacks, T., Hacohen, N., Bernstein, B. E., Kellis, M., Regev, A., Rinn, J. L. and Lander, E. S. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458, 223–227. doi: 10.1038/nature07672.Google Scholar
Hayden, M. S. and Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell 132, 344–362. doi: 10.1016/j.cell.2008.01.020.Google Scholar
Hayward, A. R., Chmura, K. and Cosyns, M. (2000). Interferon-gamma is required for innate immunity to Cryptosporidium parvum in mice. Journal of Infectious Diseases 182, 1001–1004. doi: 10.1086/315802.Google Scholar
Hu, G., Zhou, R., Liu, J., Gong, A. Y., Eischeid, A. N., Dittman, J. W. and Chen, X. M. (2009). MicroRNA-98 and let-7 confer cholangiocyte expression of cytokine-inducible Src homology 2-containing protein in response to microbial challenge. Journal of Immunology 183, 1617–1624. doi: 10.4049/jimmunol.0804362.Google Scholar
Hu, G., Zhou, R., Liu, J., Gong, A. Y. and Chen, X. M. (2010). MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling 4 in biliary epithelial cells in response to Cryptosporidium parvum infection. Journal of Infectious Diseases 202, 125–135. doi: 10.1086/653212.Google Scholar
Hu, G., Gong, A. Y., Roth, A. L., Huang, B. Q., Ward, H. D., Zhu, G., Larusso, N. F., Hanson, N. D. and Chen, X. M. (2013). Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense. PLoS Pathogens 9, e1003261. doi: 10.1371/journal.ppat.1003261.Google Scholar
Huarte, M., Guttman, M., Feldser, D., Garber, M., Koziol, M. J., Kenzelmann-Broz, D., Khalil, A. M., Zuk, O., Amit, I., Rabani, M., Attardi, L. D., Regev, A., Lander, E. S., Jacks, T. and Rinn, J. L. (2010). A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142, 409–419. doi: 10.1016/j.cell.2010.06.040.Google Scholar
Kawai, T. and Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology 11, 373–384. doi: 10.1038/ni.1863.Google Scholar
Kincaid, R. P. and Sullivan, C. S. (2012). Virus-encoded microRNAs: an overview and a look to the future. PLoS Pathogens 8, e1003018. doi: 10.1371/journal.ppat.1003018.Google Scholar
Korbel, D. S., Barakat, F. M., Di Santo, J. P. and McDonald, V. (2011). CD4+ T cells are not essential for control of early acute Cryptosporidium parvum infection in neonatal mice. Infection and Immunity 79, 1647–1653. doi: 10.1128/IAI.00922-10.Google Scholar
Kotloff, K. L., Nataro, J. P., Blackwelder, W. C., Nasrin, D., Farag, T. H., Panchalingam, S., Wu, Y., Sow, S. O., Sur, D., Breiman, R. F., Faruque, A. S., Zaidi, A. K., Saha, D., Alonso, P. L., Tamboura, B., Sanogo, D., Onwuchekwa, U., Manna, B., Ramamurthy, T., Kanungo, S., Ochieng, J. B., Omore, R., Oundo, J. O., Hossain, A., Das, S. K., Ahmed, S., Qureshi, S., Quadri, F., Adegbola, R. A., Antonio, M., Hossain, M. J., Akinsola, A., Mandomando, I., Nhampossa, T., Acácio, S., Biswas, K., O'Reilly, C. E., Mintz, E. D., Berkeley, L. Y., Muhsen, K., Sommerfelt, H., Robins-Browne, R. M. and Levine, M. M. (2013). Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382, 209–222. doi: 10.1016/S0140-6736(13)60844-2.Google Scholar
Kozomara, A. and Griffiths-Jones, S. (2011). miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Research 39, D152–D157. doi: 10.1093/nar/gkq1027.Google Scholar
Lean, I. S., McDonald, S. A., Bajaj-Elliott, M., Pollok, R. C., Farthing, M. J. and McDonald, V. (2003). Interleukin-4 and transforming growth factor beta have opposing regulatory effects on gamma interferon-mediated inhibition of Cryptosporidium parvum reproduction. Infection and Immunity 71, 4580–4585. doi: 10.1128/IAI.71.8.4580-4585.2003.Google Scholar
Lee, J. T. (2012). Epigenetic regulation by long noncoding RNAs. Science 338, 1435–1439. doi: 10.1126/science.1231776.Google Scholar
Lee, Y., Kim, M., Han, J., Yeom, K. H., Lee, S., Baek, S. H. and Kim, V. N. (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO Journal 23, 4051–4060. doi: 10.1038/sj.emboj.7600385.Google Scholar
Leitch, G. J. and He, Q. (1994). Arginine-derived nitric oxide reduces fecal oocyst shedding in nude mice infected with Cryptosporidium parvum . Infection and Immunity 62, 5173–5176.CrossRefGoogle ScholarPubMed
Leung, A. K., Young, A. G., Bhutkar, A., Zheng, G. X., Bosson, A. D., Nielsen, C. B. and Sharp, P. A. (2011). Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs. Nature Structural and Molecular Biology 18, 237–244. doi: 10.1038/nsmb.1991.Google Scholar
Linker, K., Pautz, A., Fechir, M., Hubrich, T., Greeve, J. and Kleinert, H. (2005). Involvement of KSRP in the post-transcriptional regulation of human iNOS expression-complex interplay of KSRP with TTP and HuR. Nucleic Acids Research 33, 4813–4827. doi: 10.1093/nar/gki797.Google Scholar
Liu, N. and Olson, E. N. (2010). MicroRNA regulatory networks in cardiovascular development. Developmental Cell 18, 510–525. doi: 10.1016/j.devcel.2010.03.010.CrossRefGoogle ScholarPubMed
Mallegol, J., Van Niel, G., Lebreton, C., Lepelletier, Y., Candalh, C., Dugave, C., Heath, J. K., Raposo, G., Cerf-Bensussan, N. and Heyman, M. (2007). T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology 132, 1866–1876. doi: 10.1053/j.gastro.2007.02.043.Google Scholar
Mansell, A., Smith, R., Doyle, S. L., Gray, P., Fenner, J. E., Crack, P. J., Nicholson, S. E., Hilton, D. J., O'Neill, L. A. and Hertzog, P. J. (2006). Suppressor of cytokine signaling 1 negatively regulates toll-like receptor signaling by mediating Mal degradation. Nature Immunology 7, 148–155. doi: 10.1038/ni1299.Google Scholar
McDonald, V., Korbel, D. S., Barakat, F. M., Choudhry, N. and Petry, F. (2013). Innate immune responses against Cryptosporidium parvum infection. Parasite Immunology 35, 55–64. doi: 10.1111/pim.12020.Google Scholar
Mercer, T. R., Dinger, M. E. and Mattick, J. S. (2009). Long non-coding RNAs: insights into functions. Nature Reviews Genetics 10, 155–159. doi: 10.1038/nrg2521.Google Scholar
Muller, W. A. (2009). Mechanisms of transendothelial migration of leukocytes. Circulation Research 105, 223–230. doi: 10.1161/CIRCRESAHA.109.200717.Google Scholar
Nordone, S. K. and Gookin, J. L. (2010). Lymphocytes and not IFN-gamma mediate expression of iNOS by intestinal epithelium in murine cryptosporidiosis. Parasitology Research 106, 1507–1511. doi: 10.1007/s00436-010-1837-7.CrossRefGoogle Scholar
O'Hara, S. P., Splinter, P. L., Gajdos, G. B., Trussoni, C. E., Fernandez-Zapico, M. E., Chen, X. M. and LaRusso, N. F. (2010). NFkappaB p50-CCAAT/enhancer-binding protein beta (C/EBPbeta)-mediated transcriptional repression of microRNA let-7i following microbial infection. Journal of Biological Chemistry 285, 216–225. doi: 10.1074/jbc.M109.041640.CrossRefGoogle Scholar
Ørom, U. A. and Lund, A. H. (2010). Experimental identification of microRNA targets. Gene 451, 1–5. doi: 10.1016/j.gene.2009.11.008.Google Scholar
Pantenburg, B., Dann, S. M., Wang, H. C., Robinson, P., Castellanos-Gonzalez, A., Lewis, D. E. and White, A. C. Jr. (2008). Intestinal immune response to human Cryptosporidium sp. infection. Infection and Immunity 76, 23–29. doi: 10.1128/IAI.00960-07.Google Scholar
Pautz, A., Art, J., Hahn, S., Nowag, S., Voss, C. and Kleinert, H. (2010). Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 23, 75–93. doi: 10.1016/j.niox.2010.04.007.Google Scholar
Petry, F., Jakobi, V. and Tessema, T. S. (2010). Host immune response to Cryptosporidium parvum infection. Experimental Parasitology 126, 304–309. doi: 10.1016/j.exppara.2010.05.022.Google Scholar
Pierce, K. K. and Kirkpatrick, B. D. (2009). Update on human infections caused by intestinal protozoa. Current Opinion in Gastroenterology 25, 12–17. doi: 10.1097/MOG.0b013e32831da7dd.Google Scholar
Poppelmann, B., Klimmek, K., Strozyk, E., Voss, R., Schwarz, T. and Kulms, D. (2005). NF{kappa}B-dependent down-regulation of tumor necrosis factor receptor-associated proteins contributes to interleukin-1-mediated enhancement of ultraviolet B-induced apoptosis. Journal of Biological Chemistry 280, 15635–15643. doi: 10.1074/jbc.M413006200.Google Scholar
Putignani, L. and Menichella, D. (2010). Global distribution, public health and clinical impact of the protozoan pathogen cryptosporidium. Interdisciplinary Perspectives on Infectious Diseases 2010, 1–39. doi: 10.1155/2010/753512.CrossRefGoogle ScholarPubMed
Reigstad, C. S., Lunden, G. O., Felin, J. and Backhed, F. (2009). Regulation of serum amyloid A3 (SAA3) in mouse colonic epithelium and adipose tissue by the intestinal microbiota. PLoS One 4, e5842. doi: 10.1371/journal.pone.0005842.Google Scholar
Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P. J., Segal, E. and Chang, H. Y. (2007). Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311–1323. doi: 10.1016/j.cell.2007.05.022.Google Scholar
Robbins, P. D. and Morelli, A. E. (2014). Regulation of immune responses by extracellular vesicles. Nature Review in Immunology 105, 195–208. doi: 10.1038/nri3622.Google Scholar
Saini, H. K., Griffiths-Jones, S. and Enright, A. J. (2007). Genomic analysis of human microRNA transcripts. Proceedings of the National Academy of Sciences USA 104, 17719–17724. doi: 10.1073/pnas.0703890104.Google Scholar
Schonrock, N., Harvey, R. P. and Mattick, J. S. (2012). Long noncoding RNAs in cardiac development and pathophysiology. Circulation Research 111, 1349–1362. doi: 10.1161/CIRCRESAHA.112.268953.Google Scholar
Smalheiser, N. R. (2007). Exosomal transfer of proteins and RNAs at synapses in the nervous system. Biology Direct 2, 35. doi: 10.1186/1745-6150-2-35.Google Scholar
Stievano, L., Piovan, E. and Amadori, A. (2004). C and CX3C chemokines: cell sources and physiopathological implications. Critical Reviews in Immunology 24, 205–228. doi: 10.1615/CritRevImmunol.v24.i3.40.Google Scholar
Striepen, B. (2013). Parasitic infections: time to tackle cryptosporidiosis. Nature 503, 189–191. doi: 10.1038/503189a.Google Scholar
Südhof, T. C. and Rothman, J. E. (2009). Membrane fusion: grappling with SNARE and SM proteins. Science 323, 474–477. doi: 10.1126/science.1161748.Google Scholar
Taganov, K. D., Boldin, M. P., Chang, K. J. and Baltimore, D. (2006). NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings of the National Academy of Sciences USA 103, 12481–12486. doi: 10.1073/pnas.0605298103.Google Scholar
Tang, B., Xiao, B., Liu, Z., Li, N., Zhu, E. D., Li, B. S., Xie, Q. H., Zhuang, Y., Zou, Q. M. and Mao, X. H. (2010). Identification of MyD88 as a novel target of miR-155, involved in negative regulation of Helicobacter pylori-induced inflammation. FEBS Letters 584, 1481–1486. doi: 10.1016/j.febslet.2010.02.063.Google Scholar
Théry, C. (2011). Exosomes: secreted vesicles and intercellular communications. F1000 Biology Reports 3, 15. doi: 10.3410/B3-15.Google Scholar
Tzipori, S. and Griffiths, J. K. (1998). Natural history and biology of Cryptosporidium parvum . Advances in Parasitology 40, 5–36.Google Scholar
Ulitsky, I. and Bartel, D. P. (2013). LincRNAs: genomics, evolution, and mechanisms. Cell 154, 26–46. doi: 10.1016/j.cell.2013.06.020.Google Scholar
Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J. J. and Lötvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology 9, 654–659. doi: 10.1038/ncb1596.Google Scholar
van Niel, G., Porto-Carreiro, I., Simoes, S. and Raposo, G. (2006). Exosomes: a common pathway for a specialized function. Journal of Biochemistry 140, 13–21. doi: 10.1093/jb/mvj128.Google Scholar
Winter, J., Jung, S., Keller, S., Gregory, R. I. and Diederichs, S. (2009). Many roads to maturity: microRNA biogenesis pathways and their regulation. Nature Cell Biology 11, 228–234. doi: 10.1038/ncb0309-228.Google Scholar
Winzen, R., Thakur, B. K., Dittrich-Breiholz, O., Shah, M., Redich, N., Dhamija, S., Kracht, M. and Holtmann, H. (2007). Functional analysis of KSRP interaction with the AU-rich element of interleukin-8 and identification of inflammatory mRNA targets. Molecular and Cellular Biology 27, 8388–8400. doi: 10.1128/MCB.01493-07.Google Scholar
Yoshimura, A., Naka, T. and Kubo, M. (2007). SOCS proteins, cytokine signalling and immune regulation. Nature Reviews Immunology 7, 454–465. doi: 10.1038/nri2093.Google Scholar
Yu, X., Harris, S. L. and Levine, A. J. (2006). The regulation of exosome secretion: a novel function of the p53 protein. Cancer Research 66, 4795–4801. doi: 10.1158/0008-5472.CAN-05-4579.Google Scholar
Zhou, R., Hu, G., Liu, J., Gong, A. Y., Drescher, K. M. and Chen, X. M. (2009). NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS Pathogens 5, e1000681. doi: 10.1371/journal.ppat.1000681.Google Scholar
Zhou, R., O'Hara, S. P. and Chen, X. M. (2011). MicroRNA regulation of innate immune responses in epithelial cells. Cellular and Molecular Immunology 8, 371–379. doi: 10.1038/cmi.2011.19.Google Scholar
Zhou, R., Gong, A. Y., Eischeid, A. N. and Chen, X. M. (2012). miR-27b targets KSRP to coordinate TLR4-mediated epithelial defense against Cryptosporidium parvum infection. PLoS Pathogens 8, e1002702. doi: 10.1371/journal.ppat.1002702.Google Scholar
Zhou, R., Gong, A. Y., Chen, D., Miller, R. E., Eischeid, A. N. and Chen, X. M. (2013). Histone deacetylases and NF-kB signaling coordinate expression of CX3CL1 in epithelial cells in response to microbial challenge by suppressing miR-424 and miR-503. PLoS One 8, e65153. doi: 10.1371/journal.pone.0065153.Google Scholar