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* Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan;
Department of Dermatology,
Center for Anatomical Studies, and
Laboratory of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; and
¶ Laboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
Delayed-type hypersensitivity represents high levels of protein Ag-specific adaptive immunity induced by mycobacterial infection, and can be monitored in the Ag-challenged skin. Besides protein Ags, recent evidence has suggested that a substantial immunity directed against glycolipid Ags is also elicited in response to mycobacterial infection, but skin hypersensitivity to this class of Ags has not been fully assessed. To address this issue directly, glycolipid-specific skin reactions were evaluated in guinea pigs infected with Mycobacterium avium complex (MAC). Significant skin induration was observed in MAC-infected, but not mock-infected, guinea pigs, following intradermal administration of a mixture of MAC-derived glycolipids. Surprisingly, this glycolipid-specific skin response involved up-regulated expression of IL-5 mRNA in situ and marked local infiltration of eosinophils. Challenge experiments with individual glycolipid components detected an outstanding capability for trehalose dimycolate (TDM), but not a structurally related glycolipid, glucose monomycolate, to elicit the skin response. T lymphocytes derived from the spleen of MAC-infected, but not uninfected, guinea pigs specifically responded to TDM in vitro by up-regulating IL-5 transcription, and this response was not blocked by Abs that reacted to the known guinea pig group 1 CD1 proteins. Finally, the eosinophilic skin hypersensitivity to TDM was also elicited in guinea pigs vaccinated with bacillus Calmette-Guerin, which contrasted sharply with the classical delayed-type hypersensitivity response to the purified protein derivative. Therefore, the TDM-elicited eosinophilic response defines a new form of hypersensitivity in mycobacterial infection, which may account for local infiltration of eosinophils often observed at the site of infection.
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1 This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid from Scientific Research on Priority Areas) (to M.S.), and from the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (B) (to M.S.) and (C) (to I.M.)).
2 Address correspondence and reprint requests to Prof. Masahiko Sugita, M.D., Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan. E-mail address: msugita{at}virus.kyoto-u.ac.jp
3 Abbreviations used in this paper: DTH, delayed-type hypersensitivity; BCG, bacillus Calmette-Guerin; MAC, Mycobacterium avium complex; PMN, polymorphonuclear cell; PPD, purified protein derivative; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GMM, glucose monomycolate; GPL, glycopeptidolipid; TDM, trehalose dimycolate; TLC, thin layer chromatography; TMM, trehalose monomycolate.
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  H. Nakao, I. Matsunaga, D. Morita, T. Aboshi, T. Harada, Y. Nakagawa, N. Mori, and M. Sugita Mycolyltransferase from Mycobacterium leprae Excludes Mycolate-containing Glycolipid Substrates J. Biochem., November 1, 2009; 146(5): 659 - 665. [Abstract] [Full Text] [PDF]
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