title: Inflammatory monocytes hinder antiviral B cell responses.
abstract: Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b+Ly6Chiinflammatory monocytes. These myeloid cells were recruited to lymph nodes draining LCMV infection sites in a type I interferon-, CCR2-dependent fashion and they suppressed antiviral B cell responses by virtue of their ability to produce nitric oxide. Depletion of inflammatory monocytes, inhibition of their lymph node recruitment or impairment of their nitric oxide-producing ability enhanced LCMV-specific B cell survival and led to robust neutralizing antibody production. In conclusion, our results identify inflammatory monocytes as critical gatekeepers that prevent antiviral B cell responses and suggest that certain viruses take advantage of these cells to prolong their persistence within the host.
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sammicheli
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
authors.forename: Mirela
authors.initials: M
authors.lastname: Kuka
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Lucia
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Nereida Jimenez
authors.initials: NJ
authors.lastname: de Oya
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Giovanni
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Fioravanti
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cristofani
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
authors.forename: Carmela G
authors.initials: CG
authors.lastname: Maganuco
authors.affiliation: Division of Experimental Virology, Department of Biomedicine, University of Basel, Basel 4003, Switzerland.
authors.forename: Benedict
authors.initials: B
authors.lastname: Fallet
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ganzer
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sironi
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Mainetti
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) and Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milano, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Ostuni
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Larimore
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: de la Torre
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Luca G
authors.initials: LG
authors.lastname: Guidotti
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy; Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Iannacone