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*AIDS
*Cryptosporidiosis

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Infection and Immunity, January 2007, p. 481-487, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01237-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

High Levels of CXCL10 Are Produced by Intestinal Epithelial Cells in AIDS Patients with Active Cryptosporidiosis but Not after Reconstitution of Immunity{triangledown}

Heuy-Ching Wang,1 Sara M. Dann,1 Pablo C. Okhuysen,2 Dorothy E. Lewis,3 Cynthia L. Chappell,2 Douglas G. Adler,2,{dagger} and A. Clinton White Jr.1,3*

Infectious Disease Section, Department of Medicine,1 Department of Immunology, Baylor College of Medicine,3 School of Public Health and School of Medicine, University of Texas Health Sciences Center, Houston, Texas2

Received 3 August 2006/ Returned for modification 16 September 2006/ Accepted 4 October 2006

Chemokines play key roles in attracting immune cells to sites of infections. However, few data on chemokine expression in the gut during human infections are available. We examined expression of chemokines in intestinal tissues of AIDS patients during active Cryptosporidium infection and during resolution of such an infection. The chemokines and cytokines in cell lysates from jejunal biopsy tissues were assayed by a 22-multiplex bead immunoassay. CXCL10 (IP-10) and its receptor, CXCR3, in sections were studied by immunohistochemistry. In biopsies from AIDS patients with active cryptosporidiosis, four chemokines (CXCL10, CCL11 [eotaxin], CCL5 [RANTES], and CCL2 [monocyte chemoattractant protein 1]) and three cytokines (interleukin-1{alpha} [IL-1{alpha}], IL-10, and granulocyte colony-stimulating factor) were detected. The level of CXCL10 was significantly increased in AIDS patients with cryptosporidiosis compared to the level in AIDS patients without cryptosporidiosis or in normal volunteers (median in AIDS patients with cryptosporidiosis, 508 pg/mg protein, compared to 111 pg/mg and 72 pg/mg protein in AIDS patients without cryptosporidiosis and in normal volunteers, respectively [P < 0.05 and P < 0.005, respectively, as determined by a Mann-Whitney test]). The level of CXCL10 correlated with the parasite burden (as measured by the number of Cryptosporidium oocysts in the stools) and also with the IL-1{alpha} concentration (Pearson correlation values, 0.961 [P < 0.01] and 0.737 [P < 0.05]). As determined by immunohistochemistry, CXCL10 localized to epithelial cells at the site of infection. Following effective antiparasite and antiretroviral therapy, Cryptosporidium infections resolved, and the levels of CXCL10 decreased to normal levels. We hypothesized that CXCL10 plays an important role in the resolution of cryptosporidiosis by attracting immune effector cells to the site of infection. By contrast, in AIDS patients lacking effector cells, CXCL10 may contribute to the immunopathogenesis by recruiting inflammatory cells.

* Corresponding author. Mailing address: Infectious Disease Section, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, 525D, Houston, TX 77030. Phone: (713) 798-6846. Fax: (713) 790-0681. E-mail: arthurw{at}bcm.tmc.edu.

{triangledown} Published ahead of print on 16 October 2006.

Editor: W. A. Petri, Jr.

{dagger} Present address: Division of Gastroenterology, University of Utah, Salt Lake City, UT.

Infection and Immunity, January 2007, p. 481-487, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01237-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pantenburg, B., Dann, S. M., Wang, H.-C., Robinson, P., Castellanos-Gonzalez, A., Lewis, D. E., White, A. C. Jr. (2008). Intestinal Immune Response to Human Cryptosporidium sp. Infection. Infect. Immun. 76: 23-29 [Full Text]  


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