title: High levels of CXCL10 are produced by intestinal epithelial cells in AIDS patients with active cryptosporidiosis but not after reconstitution of immunity.
abstract: 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-1alpha [IL-1alpha], 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-1alpha 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.
authors.affiliation: Infectious Disease Section, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, 525D, Houston, TX 77030, USA.
authors.forename: Heuy-Ching
authors.initials: HC
authors.lastname: Wang
authors.forename: Sara M
authors.initials: SM
authors.lastname: Dann
authors.forename: Pablo C
authors.initials: PC
authors.lastname: Okhuysen
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Lewis
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Chappell
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Adler
authors.forename: A Clinton
authors.initials: AC
authors.lastname: White
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000977:Antiparasitic Agents / Q000627:therapeutic use; D054357:Chemokine CXCL10; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis*; D003457:Cryptosporidiosis / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism*; D008297:Male
chemical_list: D044966:Anti-Retroviral Agents; D000977:Antiparasitic Agents; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC