Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection

Author:

Khader Shabaana A.1,Partida-Sanchez Santiago1,Bell Guy1,Jelley-Gibbs Dawn M.1,Swain Susan1,Pearl John E.1,Ghilardi Nico2,deSauvage Frederic J.2,Lund Frances E.1,Cooper Andrea M.1

Affiliation:

1. Trudeau Institute, Inc., Saranac Lake, NY 12983

2. Genentech Inc., South San Francisco, CA 94080

Abstract

Migration of dendritic cells (DCs) to the draining lymph node (DLN) is required for the activation of naive T cells. We show here that migration of DCs from the lung to the DLN after Mycobacterium tuberculosis (Mtb) exposure is defective in mice lacking interleukin (IL)-12p40. This defect compromises the ability of IL-12p40–deficient DCs to activate naive T cells in vivo; however, DCs that express IL-12p40 alone can activate naive T cells. Treatment of IL-12p40–deficient DCs with IL-12p40 homodimer (IL-12(p40)2) restores Mtb-induced DC migration and the ability of IL-12p40–deficient DCs to activate naive T cells. These data define a novel and fundamental role for IL-12p40 in the pathogen-induced activation of pulmonary DCs.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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