title: Interplay between CD8α+ dendritic cells and monocytes in response to Listeria monocytogenes infection attenuates T cell responses.
abstract: During the course of a microbial infection, different antigen presenting cells (APCs) are exposed and contribute to the ensuing immune response. CD8α(+) dendritic cells (DCs) are an important coordinator of early immune responses to the intracellular bacteria Listeria monocytogenes (Lm) and are crucial for CD8(+) T cell immunity. In this study, we examine the contribution of different primary APCs to inducing immune responses against Lm. We find that CD8α(+) DCs are the most susceptible to infection while plasmacytoid DCs are not infected. Moreover, CD8α(+) DCs are the only DC subset capable of priming an immune response to Lm in vitro and are also the only APC studied that do so when transferred into β2 microglobulin deficient mice which lack endogenous cross-presentation. Upon infection, CD11b(+) DCs primarily secrete low levels of TNFα while CD8α(+) DCs secrete IL-12 p70. Infected monocytes secrete high levels of TNFα and IL-12p70, cytokines associated with activated inflammatory macrophages. Furthermore, co-culture of infected CD8α(+) DCs and CD11b+ DCs with monocytes enhances production of IL-12 p70 and TNFα. However, the presence of monocytes in DC/T cell co-cultures attenuates T cell priming against Lm-derived antigens in vitro and in vivo. This suppressive activity of spleen-derived monocytes is mediated in part by both TNFα and inducible nitric oxide synthase (iNOS). Thus these monocytes enhance IL-12 production to Lm infection, but concurrently abrogate DC-mediated T cell priming.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Dilnawaz
authors.initials: D
authors.lastname: Kapadia
authors.forename: Aida
authors.initials: A
authors.lastname: Sadikovic
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vanloubbeeck
authors.forename: Dirk
authors.initials: D
authors.lastname: Brockstedt
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fong
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000382:microbiology; D003713:Dendritic Cells / Q000166:cytology* / Q000382:microbiology; D006825:Hybridomas / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008089:Listeria monocytogenes / Q000378:metabolism*; D008088:Listeriosis / Q000097:blood*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II