Cd1d-dependent regulation of bacterial colonization in the intestine of mice

Edward E.S. Nieuwenhuis et al. J. Clin. Invest. 119:1241–1250 (2009)

Speaker: 連國廷                                                   Time: 13:00~14:00, Oct. 14, 2009

Commentator: 蕭璦莉 老師                               Place: Room 601

Abstract:

Natural killer T (NKT) cells are a heterogeneous group of T cells that share the characteristics of T and NK cells. The NKT cells recognize the MHC class I–like molecule, Cd1d, which is an antigen-presenting molecule that binds self and foreign lipids. Cd1d is expressed on a limited subset of cells including the thymocytes, professional antigen presenting cells, keratinocytes and intestinal epithelial cells (IECs). It has been shown previously that the NKT cells could contribute to the antimicrobial host responses in bacterial, parasitic, viral and fungal infections [1], and the freshly isolated human IECs and human IEC lines could present Cd1d-restricted glycolipid antigens to NKT cells [2]. To determine how the NKT cells and Cd1d impact the pathogenesis of foreign bacteria, the authors first demonstrated that the Cd1d-deficient mice were less capable of clearingPseudomonas aeruginosa from the lung [3]. They further investigated the intestinal colonization by various bacterial pathogens, and found that it was increased in the Cd1d-deficient mice, irrespective of the species of pathogens, compared to the wild-type mice. They also showed that the compositions of intestinal microbiota in the Cd1d-deficient mice were different from those of the wild-type mice. They further found that the Paneth cells, a specific type of intestinal epithelial cell secreting the antibacterial peptides cryptdins via degranulation of secretory granules, in the Cd1d-deficient mice were less able to degranulate. In addition, the oligosaccharide composition of the Paneth cell granules in the Cd1d-deficient mice has altered as examined histochemically. These results suggest that the NKT cells may be involved in the pathogenesis of intestinal bacterial infections. However, the antigens responsible for Cd1d-restricted activation of the NKT cells in the intestine remain unclear.

References:

1.     Tupin, E., Y. Kinjo, and M. Kronenberg, The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol. 2007. 5: 405-17.

2.   van de Wal, Y., et al. Delineation of a CD1d-restricted antigen presentation pathway associated with human and mouse intestinal epithelial cells. Gastroenterology. 2003. 124: 1420-31.

3.     Nieuwenhuis, E.E., et al. CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat. Med. 2002. 8:588–593.