TY - JOUR
T1 - Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice
AU - Mountford, A.P.
AU - Coulson, P.S.
AU - Hogg, K.G.
AU - Brombacher, F.
N1 - Copyright © 2001 American Society for Microbiology
PY - 2001
Y1 - 2001
N2 - Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the
skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated
protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs)
into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of
pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced
transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels
until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide
contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from
vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both
vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated
IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A
significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were
within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting
cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were
myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional
source of IL-12 in the skin.
AB - Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the
skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated
protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs)
into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of
pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced
transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels
until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide
contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from
vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both
vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated
IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A
significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were
within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting
cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were
myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional
source of IL-12 in the skin.
U2 - 10.1128/IAI.69.1.228-236.2001
DO - 10.1128/IAI.69.1.228-236.2001
M3 - Article
VL - 69
SP - 228
EP - 236
JO - Infection and Immunity
JF - Infection and Immunity
SN - 1098-5522
IS - 1
ER -