A polymorphism in the toll-like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy.
Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacterial infections, and the mutations in the TLR2 have been shown to confer the susceptibility to infection with mycobacteria. We previously reported the detection of TLR2 Arg677Trp mutation in lepromatous leprosy. Here, the events triggered by TLR2 in response to cell lysate of Mycobacterium leprae(MLL), the causative agent of leprosy, were investigated. Upon stimulation with MLL, monocytes produced TNF-alpha and Interleukin-12 (IL-12), which play a role in the innate immune response to infection. Anti-TLR2 mAb blocked greater than 50% of the MLL-induced production of IL-12. We also performed the functional study on TLR2 by measurement of IL-12 production in serum and monocytes from leprosy patients with TLR2 mutation (Arg677Trp). The monocytes obtained from patients with the TLR2 mutation, in comparison to the wild-type TLR2, is significantly less responsive to MLL. It was also confirmed that patients with TLR2 mutation showed significantly lower serum levels of IL-12, in comparing with TLR2 wild-type. Our results reveal that innate immune response of monocytes against M. lepraeis mediated by TLR2, and suggest that the mutation in the intracellular domain of TLR2 gene is associated with IL-12 production in lepromatous leprosy.
Kang
Tae Jin
TJ
Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Socho-Gu, Seoul 137-701, The Republic of Korea.
Lee
Seong Beom
SB
Chae
Gue Tae
GT
D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis*; D015440:Leprosy, Lepromatous / Q000235:genetics* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D009000:Monocytes / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12