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CD11c⁺CD8⁺ Dendritic Cells Promote Protective Immunity to Respiratory Infection with Bordetella pertussis¹

Pádraic J. Dunne^*, Barry Moran^*, Robert C. Cummins and Kingston H. G. Mills^2,*

^* Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland; and Pathology Department, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin, Ireland

CD11c⁺CD8⁺ and CD103⁺ dendritic cells (DC) have been shown to promote regulatory T cell responses and mediate tolerance in the gastrointestinal tract. These cells have also been identified in the lung, but their role in immunity to respiratory tract infection is not clear. In this study, we have used a murine model of infection with Bordetella pertussis to examine the function of DC subtypes in protective immunity in the lungs. We found a dramatic increase in the numbers of CD11c⁺CD8⁺ DC in the cervical lymph nodes within 4 h of challenge with B. pertussis and these DC could acquire particulate Ag from the upper respiratory tract. CD11c⁺CD8⁺ DC also infiltrated the lung with a peak 7 days after B. pertussis challenge. The infiltrating CD11c⁺CD8⁺ DC expressed MHC, costimulatory and activation markers indicative of mature DC. The CD11c⁺CD8⁺ DC in the cervical lymph nodes expressed IL-4 and IL-10 and lower levels of IFN-, but in the lungs expressed predominantly IFN-. Depletion of CD8⁺ cells early in infection attenuated Th1 responses in the lungs and significantly reduced bacterial clearance. Conversely, transfer of FLT3 ligand (FL)-expanded CD11c⁺CD8⁺ DC enhanced bacterial clearance, whereas GM-CSF-expanded conventional DC had no effect. The numbers of CD11c⁺CD8⁺CD103⁺ cells were also increased during the early phase of infection. Blocking CD103 function caused a significant delay in bacterial clearance and a reduction in cellular infiltration into the lungs. These findings demonstrate that CD11c⁺CD8⁺ and CD11c⁺CD103⁺DC play a protective role in mediating immunity to B. pertussis infection in the respiratory tract.

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 This work was funded by the Health Research Board of Ireland and Science Foundation Ireland.

² Address correspondence and reprint requests to Prof. Kingston H. G. Mills, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. E-mail address: Kingston.mills{at}tcd.ie

³ Abbreviations used in this paper: Treg, regulatory T; CLN, cervical lymph node; DC, dendritic cell; pDC, plasmacytoid DC; Flt3, FMS-like tyrosine kinase 3; FL, Flt3 ligand; FLB, fluorescent latex bead; MLN, mesenteric lymph nodes; i.n, intranasally; BFA, brefeldin A; TLN, thoracic lymph node.