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Infection and Immunity, May 2007, p. 2359-2365, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01812-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Immunomodulatory Effects of the Lutzomyia longipalpis Salivary Gland Protein Maxadilan on Mouse Macrophages{triangledown}

Tess M. Brodie,* Matthew C. Smith, Robin V. Morris, and Richard G. Titus

Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523

Received 14 November 2006/ Returned for modification 23 December 2006/ Accepted 21 February 2007

Infection with Leishmania major is enhanced when the sand fly Lutzomyia longipalpis salivary peptide maxadilan (MAX) is injected along with the parasite. Here we determined the effect that MAX has on the secretion of cytokines and nitric oxide (NO) and on parasite survival in macrophages (M{Phi}s). The cytokines produced by M{Phi}s can enhance a type 1 response, which will increase NO and the killing of intracellular pathogens such as L. major, or a type 2 response, leading to antibody production that is ineffective against intracellular pathogens such as L. major. A mouse macrophage cell line (RAW 264.7) was stimulated with various concentrations of MAX and lipopolysaccharide (LPS), and the supernatants were collected after 1, 2, and 3 days. Supernatants were assayed for interleukin-12p70 (IL-12p70), IL-10, IL-6, transforming growth factor ß (TGF-ß), NO, and tumor necrosis factor alpha (TNF-{alpha}). Our results indicate that the addition of MAX upregulates the cytokines associated with a type 2 response (IL-10, IL-6, and TGF-ß) but downregulates type 1 cytokines (IL-12p70 and TNF-{alpha}) and NO. MAX was also added to L. major-infected mouse peritoneal exudate cells (PECs), and the parasite load increased significantly. The enhanced parasite load correlated with decreased NO production by PECs that were stimulated with LPS and gamma interferon in the presence of MAX. The ability of MAX to foster a type 2 response, to enhance parasite survival, and to decrease NO argues that MAX may be crucial for the early survival of Leishmania in the vertebrate host, and therefore, MAX holds considerable promise as an antigenic component for a vaccine against Leishmania.

* Corresponding author. Mailing address: Department of Microbiology, Immunology and Pathology, CVMBS, Colorado State University, 1619 Campus Delivery, Fort Collins, CO 80523-1619. Phone: (970) 231-9161. Fax: (970) 491-0603. E-mail: tessbrodie{at}hotmail.com

{triangledown} Published ahead of print on 5 March 2007.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2007, p. 2359-2365, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01812-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wheat, W. H., Pauken, K. E., Morris, R. V., Titus, R. G. (2008). Lutzomyia longipalpis Salivary Peptide Maxadilan Alters Murine Dendritic Cell Expression of CD80/86, CCR7, and Cytokine Secretion and Reprograms Dendritic Cell-Mediated Cytokine Release from Cultures Containing Allogeneic T Cells. J. Immunol. 180: 8286-8298 [Abstract] [Full Text]  


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