title: Inflammatory monocytes and neutrophils are licensed to kill during memory responses in vivo.
abstract: Immunological memory is a hallmark of B and T lymphocytes that have undergone a previous encounter with a given antigen. It is assumed that memory cells mediate better protection of the host upon re-infection because of improved effector functions such as antibody production, cytotoxic activity and cytokine secretion. In contrast to cells of the adaptive immune system, innate immune cells are believed to exhibit a comparable functional effector response each time the same pathogen is encountered. Here, using mice infected by the intracellular bacterium Listeria monocytogenes, we show that during a recall bacterial infection, the chemokine CCL3 secreted by memory CD8+ T cells drives drastic modifications of the functional properties of several populations of phagocytes. We found that inflammatory ly6C+ monocytes and neutrophils largely mediated memory CD8+ T cell bacteriocidal activity by producing increased levels of reactive oxygen species (ROS), augmenting the pH of their phagosomes and inducing antimicrobial autophagy. These events allowed an extremely rapid control of bacterial growth in vivo and accounted for protective immunity. Therefore, our results provide evidence that cytotoxic memory CD8+ T cells can license distinct antimicrobial effector mechanisms of innate cells to efficiently clear pathogens.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 924, Groupe Avenir, Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Narni-Mancinelli
authors.forename: Saidi M'Homa
authors.initials: SM
authors.lastname: Soudja
authors.forename: Karine
authors.initials: K
authors.lastname: Crozat
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.forename: Pierre
authors.initials: P
authors.lastname: Gounon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
authors.forename: Grégoire
authors.initials: G
authors.lastname: Lauvau
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054405:Chemokine CCL3 / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*
chemical_list: C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3