title: Inflammatory monocytes activate memory CD8(+) T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion.
abstract: 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.
authors.affiliation: Albert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, NY 10461, USA.
authors.forename: Saïdi M'Homa
authors.initials: SM
authors.lastname: Soudja
authors.forename: Anne L
authors.initials: AL
authors.lastname: Ruiz
authors.forename: Julien C
authors.initials: JC
authors.lastname: Marie
authors.forename: Grégoire
authors.initials: G
authors.lastname: Lauvau
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010962:Plasmodium berghei / Q000276:immunology; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D000941:Antigens; D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; D019409:Interleukin-15; D020382:Interleukin-18; C494192:Ly-6C antigen, mouse; D054390:Receptors, CCR2