QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.108381v1 319/1/269    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, T. Articles by Klein, T. W. Search for Related Content PubMed PubMed Citation Articles by Lu, T. Articles by Klein, T. W.

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Cannabinoid Treatment Suppresses the T-Helper Cell-Polarizing Function of Mouse Dendritic Cells Stimulated with Legionella pneumophila Infection

Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, Florida

Marijuana cannabinoids, such as -9-tetrahydrocannabinoid (THC), suppress type 1 T-helper 1 (Th1) immunity in a variety of models, including infection with the intracellular pathogen Legionella pneumophila (Lp). To examine the cellular mechanism of this effect, bone marrow-derived dendritic cells (DCs) were purified from BALB/c mice and studied following infection and drug treatment. DCs infected in vitro with Lp were able to protect mice when injected prior to a lethal Lp infection; however, the immunization potential of the Lp-loaded cells along with Th1 cytokine production was attenuated by THC treatment at the time of in vitro infection. In addition, THC-treated and Lp-loaded DCs were poorly stimulated in culture-primed splenic CD4⁺ T cells to produce interferon-; however, this stimulating deficiency was reversed by adding recombinant interleukin (IL)-12p40 protein to the cultures. Moreover, THC treatment inhibited the expression of DC maturation markers, such as major histocompatibility complex class II and costimulatory molecules CD86 and CD40 as determined by flow cytometry and suppressed the Notch ligand, Del-ta4, as determined by reverse transcription-polymerase chain reaction. However, THC treatment did not affect other DC functions, such as intracellular killing of Lp, determined by colony-forming unit counts of bacteria, and Lp-induced apoptosis, determined by annexin V staining. In conclusion, the data suggest that THC inhibits Th1 activation by targeting essential DC functions, such as IL-12p40 secretion, maturation, and expression of costimulatory and polarizing molecules.

Address correspondence to: Dr. Thomas W. Klein, Department of Medical Microbiology and Immunology, MDC 10 University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, Florida 33612. E-mail: tklein{at}hsc.usf.edu

This article has been cited by other articles:

				H. Lu, B. L. F. Kaplan, T. Ngaotepprutaram, and N. E. Kaminski Suppression of T cell costimulator ICOS by {Delta}9-tetrahydrocannabinol J. Leukoc. Biol., February 1, 2009; 85(2): 322 - 329. [Abstract] [Full Text] [PDF]

				J. P. Buchweitz, P. W. F. Karmaus, J. R. Harkema, K. J. Williams, and N. E. Kaminski Modulation of Airway Responses to Influenza A/PR/8/34 by {Delta}9-Tetrahydrocannabinol in C57BL/6 Mice J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 675 - 683. [Abstract] [Full Text] [PDF]

				H. Xu, C. L. Cheng, M. Chen, A. Manivannan, L. Cabay, R. G. Pertwee, A. Coutts, and J. V. Forrester Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH-133 in a rodent model of autoimmune uveoretinitis J. Leukoc. Biol., September 1, 2007; 82(3): 532 - 541. [Abstract] [Full Text] [PDF]