TY - JOUR
T1 - Interleukin 1α promotes TH1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice
AU - Von Stebut, Esther
AU - Ehrchen, Jan M.
AU - Belkaid, Yasmine
AU - Kostka, Susanna Lopez
AU - Mölle, Katharina
AU - Knop, Jürgen
AU - Sunderkötter, Cord
AU - Udey, Mark C.
PY - 2003/7/21
Y1 - 2003/7/21
N2 - Protective immunity against pathogens such as Leishmania major is mediated by interleukin (IL)-12-dependent Th1-immunity. We have shown previously that skin-dendritic cells (DCs) from both resistant C57BL/6 and susceptible BALB/c mice release IL-12 when infected with L. major, and infected BALB/c DCs effectively vaccinate against leishmaniasis. To determine if cytokines other than IL-12 might influence disease outcome, we surveyed DCs from both strains for production of a variety of cytokines. Skin-DCs produced significantly less IL-1α in response to lipopolysaccharide/interferon γ or L. major when expanded from BALB/c as compared with C57BL/6 mice. In addition, IL-1α MRNA accumulation in lymph nodes of L. major-infected BALB/c mice was ∼3-fold lower than that in C57BL/6 mice. Local injections of IL-1α during the first 3 d after infection led to dramatic, persistent reductions in lesion sizes. In L. major-infected BALB/c mice, IL-1α administration resulted in increased Th1- and strikingly decreased Th2-cytokine production. IL-1α and IL-12 treatments were similarly effective, and IL-1α efficacy was strictly IL-12 dependent. These data indicate that transient local administration of IL-1α acts in conjunction with IL-12 to influence Th-development in cutaneous leishmaniasis and prevents disease progression in susceptible BALB/c mice, perhaps by enhancing DC-induced Th1-education. Differential production of IL-1 by C57BL/6 and BALB/c mice may provide a partial explanation for the disparate outcomes of infection in these mouse strains.
AB - Protective immunity against pathogens such as Leishmania major is mediated by interleukin (IL)-12-dependent Th1-immunity. We have shown previously that skin-dendritic cells (DCs) from both resistant C57BL/6 and susceptible BALB/c mice release IL-12 when infected with L. major, and infected BALB/c DCs effectively vaccinate against leishmaniasis. To determine if cytokines other than IL-12 might influence disease outcome, we surveyed DCs from both strains for production of a variety of cytokines. Skin-DCs produced significantly less IL-1α in response to lipopolysaccharide/interferon γ or L. major when expanded from BALB/c as compared with C57BL/6 mice. In addition, IL-1α MRNA accumulation in lymph nodes of L. major-infected BALB/c mice was ∼3-fold lower than that in C57BL/6 mice. Local injections of IL-1α during the first 3 d after infection led to dramatic, persistent reductions in lesion sizes. In L. major-infected BALB/c mice, IL-1α administration resulted in increased Th1- and strikingly decreased Th2-cytokine production. IL-1α and IL-12 treatments were similarly effective, and IL-1α efficacy was strictly IL-12 dependent. These data indicate that transient local administration of IL-1α acts in conjunction with IL-12 to influence Th-development in cutaneous leishmaniasis and prevents disease progression in susceptible BALB/c mice, perhaps by enhancing DC-induced Th1-education. Differential production of IL-1 by C57BL/6 and BALB/c mice may provide a partial explanation for the disparate outcomes of infection in these mouse strains.
KW - Dendritic cell
KW - IL-1
KW - Infection
KW - Leishmania major
KW - T helper cell type 1/T helper cell type 2 immune response
UR - http://www.scopus.com/inward/record.url?scp=0041488744&partnerID=8YFLogxK
U2 - 10.1084/jem.20030159
DO - 10.1084/jem.20030159
M3 - Article
C2 - 12860932
AN - SCOPUS:0041488744
SN - 0022-1007
VL - 198
SP - 191
EP - 199
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -