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Monocyte-derived DC primed with TLR agonists secrete IL-12p70 in a CD40-dependent manner under hyperthermic conditions.
J Immunother. 2006 Nov-Dec; 29(6):606-15.JI

Abstract

Fever is an evolutionarily conserved mechanism to improve survival during infection. Previous studies have shown that feverlike temperatures directly enhance the function of murine bone marrow-derived dendritic cells (DCs). In the present study, we examined the response of human monocyte-derived DC to 39.5 degrees C hyperthermia. When primed with toll-like receptor agonists or bacterial extract but not proinflammatory cytokines, hyperthermia specifically enhanced secretion of interleukin (IL)-12p70 by DC, without altering the secretion of IL-10, tumor necrosis factor alpha or IL-1beta. These DC induced significantly higher levels of T-cell proliferation and interferon gamma production in assays of antigen presentation and MLR. Endogenous heat-sock protein 70 colocalized with CD40 in DC exposed to hyperthermic conditions. Recombinant CD40-Fc fusion protein blocked the increase in IL-12p70 secretion by DC primed with bacterial extract and hyperthermia. Thus, DC primed with toll-like receptor-agonists respond to hyperthermia with increased IL-12p70 secretion, mediated by heat-shock protein binding and activation of CD40. The data have important applications for clinical immunotherapy and the mechanism of fever.

Authors+Show Affiliations

Centre for Immunology and Cancer Research, Princess Alexandra Hospital, Division of Chemical Engineering, University of Queensland, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17063123

Citation

Peng, Judy C., et al. "Monocyte-derived DC Primed With TLR Agonists Secrete IL-12p70 in a CD40-dependent Manner Under Hyperthermic Conditions." Journal of Immunotherapy (Hagerstown, Md. : 1997), vol. 29, no. 6, 2006, pp. 606-15.
Peng JC, Hyde C, Pai S, et al. Monocyte-derived DC primed with TLR agonists secrete IL-12p70 in a CD40-dependent manner under hyperthermic conditions. J Immunother. 2006;29(6):606-15.
Peng, J. C., Hyde, C., Pai, S., O'Sullivan, B. J., Nielsen, L. K., & Thomas, R. (2006). Monocyte-derived DC primed with TLR agonists secrete IL-12p70 in a CD40-dependent manner under hyperthermic conditions. Journal of Immunotherapy (Hagerstown, Md. : 1997), 29(6), 606-15.
Peng JC, et al. Monocyte-derived DC Primed With TLR Agonists Secrete IL-12p70 in a CD40-dependent Manner Under Hyperthermic Conditions. J Immunother. 2006 Nov-Dec;29(6):606-15. PubMed PMID: 17063123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monocyte-derived DC primed with TLR agonists secrete IL-12p70 in a CD40-dependent manner under hyperthermic conditions. AU - Peng,Judy C, AU - Hyde,Claire, AU - Pai,Saparna, AU - O'Sullivan,Brendan J, AU - Nielsen,Lars K, AU - Thomas,Ranjeny, PY - 2006/10/26/pubmed PY - 2007/1/4/medline PY - 2006/10/26/entrez SP - 606 EP - 15 JF - Journal of immunotherapy (Hagerstown, Md. : 1997) JO - J Immunother VL - 29 IS - 6 N2 - Fever is an evolutionarily conserved mechanism to improve survival during infection. Previous studies have shown that feverlike temperatures directly enhance the function of murine bone marrow-derived dendritic cells (DCs). In the present study, we examined the response of human monocyte-derived DC to 39.5 degrees C hyperthermia. When primed with toll-like receptor agonists or bacterial extract but not proinflammatory cytokines, hyperthermia specifically enhanced secretion of interleukin (IL)-12p70 by DC, without altering the secretion of IL-10, tumor necrosis factor alpha or IL-1beta. These DC induced significantly higher levels of T-cell proliferation and interferon gamma production in assays of antigen presentation and MLR. Endogenous heat-sock protein 70 colocalized with CD40 in DC exposed to hyperthermic conditions. Recombinant CD40-Fc fusion protein blocked the increase in IL-12p70 secretion by DC primed with bacterial extract and hyperthermia. Thus, DC primed with toll-like receptor-agonists respond to hyperthermia with increased IL-12p70 secretion, mediated by heat-shock protein binding and activation of CD40. The data have important applications for clinical immunotherapy and the mechanism of fever. SN - 1524-9557 UR - https://www.unboundmedicine.com/medline/citation/17063123/Monocyte_derived_DC_primed_with_TLR_agonists_secrete_IL_12p70_in_a_CD40_dependent_manner_under_hyperthermic_conditions_ L2 - https://doi.org/10.1097/01.cji.0000211308.82997.4e DB - PRIME DP - Unbound Medicine ER -