In Vivo Microbial Stimulation Induces Rapid CD40 Ligand-independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas Export

@article{citeulike:1525483, abstract = {The early induction of interleukin (IL)-12 is a critical event in determining the development of both innate resistance and adaptive immunity to many intracellular pathogens. Previous in vitro studies have suggested that the macrophage (M[Phi]) is a major source of the initial IL-12 produced upon microbial stimulation and that this response promotes the differentiation of protective T helper cell 1 (Th1) CD4+ lymphocytes from precursors that are primed on antigen-bearing dendritic cells (DC). Here, we demonstrate by immunolocalization experiments and flow cytometric analysis that, contrary to expectation, DC and not M[Phi] are the initial cells to synthesize IL-12 in the spleens of mice exposed in vivo to an extract of Toxoplasma gondii or to lipopolysaccharide, two well characterized microbial stimulants of the cytokine. Importantly, this production of IL-12 occurs very rapidly and is independent of interferon [gamma] priming or of signals from T cells, such as CD40 ligand. IL-12 production by splenic DC is accompanied by an increase in number of DCs, as well as a redistribution to the T cell areas and the acquisition of markers characteristic of interdigitating dendritic cells. The capacity of splenic DC but not M[Phi] to synthesize de novo high levels of IL-12 within hours of exposure to microbial products in vivo, as well as the ability of the same stimuli to induce migration of DC to the T cell areas, argues that DC function simultaneously as both antigen-presenting cells and IL-12 producing accessory cells in the initiation of cell-mediated immunity to intracellular pathogens. This model avoids the need to invoke a three-cell interaction for Th1 differentiation and points to the DC as both a sentinel for innate recognition and the dictator of class selection in the subsequent adaptive response. 10.1084/jem.186.11.1819}, author = {Sousa, Caetano R. and Hieny, Sara and Scharton-Kersten, Tanya and Jankovic, Dragana and Charest, Hugues and Germain, Ronald N. and Sher, Alan}, citeulike-article-id = {1525483}, citeulike-linkout-0 = {http://dx.doi.org/10.1084/jem.186.11.1819}, citeulike-linkout-1 = {http://www.jem.org/cgi/content/abstract/186/11/1819}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/9382881}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=9382881}, day = {1}, doi = {10.1084/jem.186.11.1819}, journal = {J. Exp. Med.}, keywords = {dc}, month = {December}, number = {11}, pages = {1819--1829}, posted-at = {2007-07-31 17:39:26}, priority = {2}, title = {In Vivo Microbial Stimulation Induces Rapid CD40 Ligand-independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas}, url = {http://dx.doi.org/10.1084/jem.186.11.1819}, volume = {186}, year = {1997} }

TY - JOUR ID - citeulike:1525483 L3 - citeulike-article-id:1525483 N2 - The early induction of interleukin (IL)-12 is a critical event in determining the development of both innate resistance and adaptive immunity to many intracellular pathogens. Previous in vitro studies have suggested that the macrophage (M[Phi]) is a major source of the initial IL-12 produced upon microbial stimulation and that this response promotes the differentiation of protective T helper cell 1 (Th1) CD4+ lymphocytes from precursors that are primed on antigen-bearing dendritic cells (DC). Here, we demonstrate by immunolocalization experiments and flow cytometric analysis that, contrary to expectation, DC and not M[Phi] are the initial cells to synthesize IL-12 in the spleens of mice exposed in vivo to an extract of Toxoplasma gondii or to lipopolysaccharide, two well characterized microbial stimulants of the cytokine. Importantly, this production of IL-12 occurs very rapidly and is independent of interferon [gamma] priming or of signals from T cells, such as CD40 ligand. IL-12 production by splenic DC is accompanied by an increase in number of DCs, as well as a redistribution to the T cell areas and the acquisition of markers characteristic of interdigitating dendritic cells. The capacity of splenic DC but not M[Phi] to synthesize de novo high levels of IL-12 within hours of exposure to microbial products in vivo, as well as the ability of the same stimuli to induce migration of DC to the T cell areas, argues that DC function simultaneously as both antigen-presenting cells and IL-12 producing accessory cells in the initiation of cell-mediated immunity to intracellular pathogens. This model avoids the need to invoke a three-cell interaction for Th1 differentiation and points to the DC as both a sentinel for innate recognition and the dictator of class selection in the subsequent adaptive response. 10.1084/jem.186.11.1819 IS - 11 JF - J. Exp. Med. EP - 1829 TI - In Vivo Microbial Stimulation Induces Rapid CD40 Ligand-independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas VL - 186 SP - 1819 KW - dc AU - Sousa, Caetano AU - Hieny, Sara AU - Scharton-Kersten, Tanya AU - Jankovic, Dragana AU - Charest, Hugues AU - Germain, Ronald AU - Sher, Alan PY - 1997/12/01/ UR - http://dx.doi.org/10.1084/jem.186.11.1819 ER -