TY - JOUR
T1 - Cross-presenting dendritic cells are required for control of Leishmania major infection
AU - Ashok, Devika
AU - Schuster, Steffen
AU - Ronet, Catherine
AU - Rosa, Muriel
AU - Mack, Vanessa
AU - Lavanchy, Christine
AU - Marraco, Silvia F.
AU - Fasel, Nicolas
AU - Murphy, Kenneth M.
AU - Tacchini-Cottier, Fabienne
AU - Acha-Orbea, Hans
PY - 2014/5
Y1 - 2014/5
N2 - Leishmania major infection induces self-healing cutaneous lesions in C57BL/6 mice. Both IL-12 and IFN-γ are essential for the control of infection. We infected Jun dimerization protein p21SNFT (Batf3-/-) mice (C57BL/6 background) that lack the major IL-12 producing and cross-presenting CD8α+ and CD103+ DC subsets. Batf3-/- mice displayed enhanced susceptibility with larger lesions and higher parasite burden. Additionally, cells from draining lymph nodes of infected Batf3-/- mice secreted less IFN-γ, but more Th2- and Th17-type cytokines, mirrored by increased serum IgE and Leishmania-specific immunoglobulin 1 (Th2 indicating). Importantly, CD8α+ DCs isolated from lymph nodes of L. major-infected mice induced significantly more IFN-γ secretion by L. major-stimulated immune T cells than CD103+ DCs. We next developed CD11c-diptheria toxin receptor: Batf3-/- mixed bone marrow chimeras to determine when the DCs are important for the control of infection. Mice depleted of Batf-3-dependent DCs from day 17 or wild-type mice depleted of cross-presenting DCs from 17-19 days after infection maintained significantly larger lesions similar to mice whose Batf-3-dependent DCs were depleted from the onset of infection. Thus, we have identified a crucial role for Batf-3-dependent DCs in protection against L. major.
AB - Leishmania major infection induces self-healing cutaneous lesions in C57BL/6 mice. Both IL-12 and IFN-γ are essential for the control of infection. We infected Jun dimerization protein p21SNFT (Batf3-/-) mice (C57BL/6 background) that lack the major IL-12 producing and cross-presenting CD8α+ and CD103+ DC subsets. Batf3-/- mice displayed enhanced susceptibility with larger lesions and higher parasite burden. Additionally, cells from draining lymph nodes of infected Batf3-/- mice secreted less IFN-γ, but more Th2- and Th17-type cytokines, mirrored by increased serum IgE and Leishmania-specific immunoglobulin 1 (Th2 indicating). Importantly, CD8α+ DCs isolated from lymph nodes of L. major-infected mice induced significantly more IFN-γ secretion by L. major-stimulated immune T cells than CD103+ DCs. We next developed CD11c-diptheria toxin receptor: Batf3-/- mixed bone marrow chimeras to determine when the DCs are important for the control of infection. Mice depleted of Batf-3-dependent DCs from day 17 or wild-type mice depleted of cross-presenting DCs from 17-19 days after infection maintained significantly larger lesions similar to mice whose Batf-3-dependent DCs were depleted from the onset of infection. Thus, we have identified a crucial role for Batf-3-dependent DCs in protection against L. major.
KW - Batf-3
KW - Leishmania major
UR - http://www.scopus.com/inward/record.url?scp=84899530490&partnerID=8YFLogxK
U2 - 10.1002/eji.201344242
DO - 10.1002/eji.201344242
M3 - Article
C2 - 24643576
AN - SCOPUS:84899530490
SN - 0014-2980
VL - 44
SP - 1422
EP - 1432
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 5
ER -