TY - JOUR
T1 - Inflammatory Monocytes Activate Memory CD8+ T and Innate NK Lymphocytes Independent of Cognate Antigen during Microbial Pathogen Invasion
AU - Soudja, Saïdi M.Homa
AU - Ruiz, Anne L.
AU - Marie, Julien C.
AU - Lauvau, Grégoire
N1 - Funding Information:
H2-K d /LLO 91-99 tetramers came from the NIH Tetramer Facility. We are grateful to W. Jacobs, Jr. for privileged access to the HHMI Aria II and thank L. Tesfa (FACS Core). We thank F. Sutterwala (University of Iowa) and R. Flavell (Yale University) for providing Casp1 −/− bone-marrow cells and mice; D. Woodland and J. Kohlmeier (Trudeau Institute) for providing Ifnar1 −/− bone marrow cells; T. Moran (Mount Sinai School of Medecine) for Irf3 −/− mice; and E. Pamer (Memorial Sloan-Kettering Cancer Center) for CCR2-DTR and WP20 mice. We thank C. Biron (Brown University) for providing stocks of MCMV. We thank M. Bajénoff (CIML, France), S. Porcelli (AECOM, NY), L. Chorro, C. Chandrabos, and E. Spaulding for helpful discussions. This work was supported by Institutional Funds of the Albert Einstein College of Medicine of Yeshiva University (G.L.), the National Institute of Health (R21AI095835, G.L.), the Agence Nationale pour la Recherche (ANR-10-LABX-61, J.M.), InCa Atip/Avenir (J.M.), and the fundation Bettencourt-Schueller (J.M.). Core flow cytometry were supported by the Albert Einstein Cancer Center (NCI Grant 2P30CA013330). S.M.S. designed the study, performed experiments, and analyzed data. A.R. and J.M. performed and analyzed the LCMV experiments and commented on the manuscript. G.L. designed the study, analyzed the data, and wrote the paper.
PY - 2012/9/21
Y1 - 2012/9/21
N2 - Memory CD8+ T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8+ T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. Here, we show that Ly6C+CCR2+ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8+ T and NK lymphocytes activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. Memory CD8+ T cells became potent effector cells by sensing inflammation from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral, and parasitic infections, and contributed to innate responses and protection in vivo. Thus, inflammatory monocyte-derived IL-18 and IL-15 are critical to initiate memory CD8+ T and NK lymphocytes differentiation into antimicrobial effector cells.
AB - Memory CD8+ T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8+ T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. Here, we show that Ly6C+CCR2+ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8+ T and NK lymphocytes activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. Memory CD8+ T cells became potent effector cells by sensing inflammation from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral, and parasitic infections, and contributed to innate responses and protection in vivo. Thus, inflammatory monocyte-derived IL-18 and IL-15 are critical to initiate memory CD8+ T and NK lymphocytes differentiation into antimicrobial effector cells.
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U2 - 10.1016/j.immuni.2012.05.029
DO - 10.1016/j.immuni.2012.05.029
M3 - Article
C2 - 22940097
AN - SCOPUS:84866489404
SN - 1074-7613
VL - 37
SP - 549
EP - 562
JO - Immunity
JF - Immunity
IS - 3
ER -