Frontiers in immunology and immune tolerance: new perspectives

Abstract

molecules, constitutively expressed on all nucleated cells, attenuate TLR-triggered production of inflammatory cytokines and type I interferon from macrophages by interacting with tyrosine kinase Fps/Fes which subsequently activates phosphatase SHP-2 to inhibit TLR signaling. MHC I/ Fps/SHP-2 pathways may be involved in the maintenances of macrophage quiescent and in the fine tune of TLR-triggered immune responses during infections, adding new knowledge in the field of TLR signaling network and innate immunity. ValerieQuesniaux,ProfessorandDirector of Institute of Molecular and Experimental Immunology and Neurogenetics at the French Center of National Research Science (CNRS), then presented updates to the role of MyD88 and interleukin-1 receptor (IL-1R) pathways in host response to Mycobacterium tuberculosis (MTB) infection. It has been known that mycobacteria produce a large variety of agonists for TLRs such as TLR2 and TLR4, but gene disruption inTLR2,TLR4,andTLR9onlyslightlyimpairs the long-term control of MTB infection, with little effect on acute infection. However, MyD88, the common adapter involved in TLRs, IL-1, and IL-18 receptor signal, is essential for the control of acute MTB infection. It is likely that this control occurs at the level of innate response since adaptive response is spared in the absence of MyD88. Dr Quesniaux then addressed the role of IL-1 and IL-18 receptor pathways in th e MyD88-dependent control of acute MTB infection. She demonstrated that the absenceofanIL-1Rsignalleadstoadramatic defect in early control of MTB infection similar to that seen in the absence of MyD88 ,w hile IL-18R is dispensable. She suggests that both IL-1 and MyD88 greatly