Glycerol monomycolate, a latent tuberculosis-associated mycobacterial lipid, induces eosinophilic hypersensitivity responses in guinea pigs |
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Authors: | Hattori Yuki Matsunaga Isamu Komori Takaya Urakawa Tetsuo Nakamura Takashi Fujiwara Nagatoshi Hiromatsu Kenji Harashima Hideyoshi Sugita Masahiko |
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Institution: | aLaboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan;bLaboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan;cFaculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan;dDepartment of Bacteriology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan;eDepartment of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan |
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Abstract: | Dynamic changes in the lipid composition of the cell wall occur in pathogenic mycobacteria that are often intended for adaptation to the host environment. Dormant mycobacteria should have evolved efficient maneuvers for cohabitation, allowing the microbes to persist for years within the host. Glycerol monomycolate (GroMM) has been implicated as a specific immune target in human individuals with latent, but not active, tuberculosis, but the in vivo response to GroMM and the relevance of it to latent infection remain poorly understood. Here, we immunized guinea pigs with bacillus Calmette–Guerin (BCG) expressing high levels of GroMM and then, monitored skin reactions at the site of challenge with GroMM-containing liposome. We found that BCG-immunized guinea pigs mounted enhanced skin reactions to GroMM with prominent local infiltration by eosinophils. Consistent with this, GroMM-stimulated lymph node cells upregulated the expression of T helper (Th)2-type cytokines, such as interleukin (IL)-5 and IL-10, that could potentially counteract the microbe-eliminating Th1-type cytokine response. On the basis of these observations, we predict that the host response to GroMM produced by dormant mycobacteria would contribute to their long-term survival in the host. |
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Keywords: | Abbreviations: BCG M bovis bacillus Calmette&ndash Guerin GAPDH glyceraldehyde-3-phosphate dehydrogenase GroMM glycerol monomycolate IFN interferon IL interleukin MA mycolic acid MN mononuclear PMN polymorphonuclear TDM trehalose dimycolate Th T helper TLC thin layer chromatography |
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