Rol de la molecula cd1d

ellular Immunology
Cellular Immunology 227 (2004) 109–120 www.elsevier.com/locate/ycimm

The role of CD1d in the immune response against Listeria infection
Victor Arrunategui-Correa and Hyun Sil Kim¤
Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA Received 28 October 2003; accepted 4 February 2004

AbstractTo address the role of CD1d in mucosal immune regulation in bacterial infection, we infected CD1d KO mice with Listeria monocytogenes (Lm). A higher systemic bacterial burden associated with inXammatory lymphocytic inWltrations within the intestine was found in CD1d KO compared with wild type (WT) mice. Lm induced strong IFN- mRNA expression in the liver of WT and the intestine of CD1d KO mice,thus demonstrating the dual, opposing immune activities of IFN- in Lm infection that is dependent on CD1d and/or NKT cells. Analysis of hepatic T cell population demonstrated a reduction of NK1.1+TCR C cells in both mice, followed by recovery only in WT mice. Last, the proportion of 4 1 integrin on lung lymphocytes from CD1d KO was dramatically increased compared with WT mice. Thus, the absenceof CD1d resulted in increased susceptibility towards Listeria infection, induced changes in NKT cells, and increased traYcking of 4 1 molecule to inXamed lung.  2004 Elsevier Inc. All rights reserved.
Keywords: CD1d; Listeria; NKT cells; IFN- ; IEL; VLA-4 integrin

1. Introduction CD1 molecules can present glycolipids rather than peptide antigens to T lymphocytes, thereby expanding theability of the adaptive immune system to rapidly recognize and respond to microbial pathogens [1,2]. Both mouse and human CD1d have been found in a variety of tissues, including the thymus, intestine, and liver [3,4]. A large fraction of NKT cells, but not all, are restricted to CD1d. Murine TCRJ 281 NK1.1+T cells, which are CD1d-restricted, have been shown to mediate important immune regulatory rolein variety of autoimmune, antitumor, and infection models [5–9]. However, it is unknown if CD1d or CD1d interacting NKT cells can actually recognize bacterial antigens. Several recent studies using various bacterial and protozoa infection models suggest that CD1d and NKT cells may be an integral component of both innate and acquired immune responses. Increased susceptibility to Borreliaburgdorferi infection in CD1d KO mice has been demonstrated along with an increased prevalence of spirochete DNA in tissues [7]. CD1d and CD1d¤

Corresponding author. Fax: 1-858-552-4327. E-mail address: hyunskim@ucsd.edu (H.S. Kim).

restricted T cells have been demonstrated to be important in the induction of Th2 response and Wbrosis related to egg deposition in murine schistosomiasis [8]. Yet,infection with Mycobacterium tuberculosis was indistinguishable in CD1d KO and WT mice [9]. Although the above mentioned studies have observed the role of CD1d in systemic microbial infection models, none of these studies had examined the role of CD1dmediated immune response in the intestine. Only one study has been published so far on the role of CD1d and NKT cells in mucosal immune systemagainst a bacterial infection. The clearance of Pseudomonas aeruginosa from the lung in an acute murine pneumonia model was shown to be CD1d-dependent, because it was impaired in CD1d deWcient mice [10]. Highlighting the immuno-modulatory role of CD1d and NKT cells in the regulation of intestinal inXammation, a recent study utilizing oxazolone, a Th2 colitis model resembling ulcerative colitis, hasshown that CD1d and TCRJ 281 NKT cells were mediating proinXammatory response via secretion of Th2 cytokines, IL-13, and to a lesser extent IL-4, when stimulated with anti-CD3/CD28 or -galactosylceramide ( -GalCer) [11]. This colitis model has identiWed intestinal lamina propria mononuclear cells from C57BL/10 mice that

0008-8749/$ - see front matter  2004 Elsevier Inc. All rights reserved....