title: Glycerol monomycolate, a latent tuberculosis-associated mycobacterial lipid, induces eosinophilic hypersensitivity responses in guinea pigs.
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.
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Isamu
authors.initials: I
authors.lastname: Matsunaga
authors.forename: Takaya
authors.initials: T
authors.lastname: Komori
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Urakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Nagatoshi
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Kenji
authors.initials: K
authors.lastname: Hiromatsu
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D055985:Latent Tuberculosis / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D050178:Monoglycerides / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D012867:Skin / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D015848:Interleukin-5; D050178:Monoglycerides; C539336:glycerol monomycolate; D016753:Interleukin-10