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Dynamics of Immune Cell Recruitment during West Nile Encephalitis and Identification of a New CD19⁺B220^–BST-2⁺ Leukocyte Population¹

Anne-Claire Bréhin^2,*,, Juliette Mouriès^2,,¶, Marie-Pascale Frenkiel, Gilles Dadaglio^,¶, Philippe Desprès, Monique Lafon^* and Thérèse Couderc^3,*,

^* Neuro-Immunologie Virale, Unité des Interactions Moléculaires Flavivirus-Hôtes, Unité de Régulation Immunitaire et Vaccinologie and Département de Biologie Cellulaire et Infection, Institut Pasteur, Paris; and ^¶ Institut National de la Santé et de la Recherche Médicale, Unité 883, Paris, France

West Nile virus (WNV) is an emerging neurotropic flavivirus. We investigated the dynamics of immune cell recruitment in peripheral tissues and in the CNS during WNV encephalitis in an immunocompetent mouse model. In the periphery, immune cell expansion can successfully limit viremia and lymphoid tissue infection. However, viral clearance in the periphery is too late to prevent viral invasion of the CNS. In the CNS, innate immune cells, including microglia/macrophages, NK cells, and plasmacytoid dendritic cells, greatly expand as the virus invades the brain, whereas B and T cells are recruited after viral invasion, and fail to control the spread of the virus. Thus, the onset of WNV encephalitis was correlated both with CNS viral infection and with a large local increase of innate immune cells. Interestingly, we identify a new immune cell type: CD19⁺B220^– BST-2⁺, which we name G8-ICs. These cells appear during peripheral infection and enter the CNS. G8-ICs express high levels of MHC class II, stain for viral Ag, and are localized in the paracortical zone of lymph nodes, strongly suggesting they are previously unidentified APCs that appear in response to viral infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ A.-C.B. performed research and analyzed and interpreted data; J.M. performed research, analyzed and interpreted data, and drafted this manuscript; M.-P.F. performed research; G.D. and P.D. analyzed and interpreted data; M.L. designed research, analyzed and interpreted data, and drafted this manuscript; and T.C. designed research, performed research, analyzed and interpreted data, and drafted this manuscript.

² A.-C.B. and J.M. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Thérèse Couderc at the current address: Microbes and Host Barriers group, Avenir Institut National de la Santé et de la Recherche Médicale, Unité 604, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, Cedex 15, France. E-mail address: tcouderc{at}pasteur.fr

⁴ Abbreviations used in this paper: WNV, West Nile virus; cDC, conventional DC; FFF, focus-forming unit; LN, lymph node; pDC, plasmacytoid DC; SB, staining buffer; MHC II, MHC class II.