Dendritic cell specific targeting of MyD88 signalling pathways in vivo.
Dendritic cells (DCs) are key regulators of both innate and adaptive immunity. During infection, DCs recognise pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs) including the Toll-like receptor (TLR) family. TLRs mainly signal via the adaptor protein MyD88. This signalling pathway is required for immune protection during many infections, which are lethal in the absence of MyD88. However, the cell type specific importance of this pathway during both innate and adaptive immune responses against pathogens in vivo remains ill-defined. We discuss recent findings from conditional KO or gain-of-function mouse models targeting TLR/MyD88 signalling pathways in DCs and other myeloid cells during infection. While the general assumption that MyD88-dependent recognition by DCs is essential for inducing protective immunity holds true in some instances, the results surprisingly indicate a much more complex context-dependent requirement for this pathway in DCs and other myeloid or lymphoid cell-types in vivo. Furthermore, we highlight the advantages of Cre-mediated DC targeting approaches and their possible limitations. We also present future perspectives on the development of new genetic mouse models to target distinct DC subsets in vivo. Such models will serve to understand the functional heterogeneity of DCs in vivo.
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), Hannover, Germany.
Catharina
C
Arnold-Schrauf
Luciana
L
Berod
Tim
T
Sparwasser
D056704:Adaptive Immunity; D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; C045073:Cre recombinase; D019426:Integrases
Cell type specific recombination; DC targeting; Infection; MyD88/TLR signalling; Transgenic mice