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Infection and Immunity, March 1999, p. 1338-1346, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Potent Immunoregulatory Effects of Salmonella typhi Flagella on Antigenic Stimulation of Human Peripheral Blood Mononuclear Cells

Timothy L. Wyant, Michael K. Tanner, and Marcelo B. Sztein*

Center for Vaccine Development, Departments of Pediatrics and Medicine, University of Maryland, Baltimore, Maryland 21201

Received 22 July 1998/Returned for modification 5 October 1998/Accepted 30 November 1998

A key function of monocytes/macrophages (Mphi ) is to present antigens to T cells. However, upon interaction with bacteria, Mphi lose their ability to effectively present soluble antigens. This functional loss was associated with alterations in the expression of adhesion molecules and CD14 and a reduction in the uptake of soluble antigen. Recently, we have demonstrated that Salmonella typhi flagella (STF) markedly decrease CD14 expression and are potent inducers of proinflammatory cytokine production by human peripheral blood mononuclear cells (hPBMC). In order to determine whether S. typhi and soluble STF also alter the ability of Mphi to activate T cells to proliferate to antigens and mitogens, hPBMC were cultured in the presence of tetanus toxoid (TT) or phytohemagglutinin (PHA) and either killed whole-cell S. typhi or purified STF protein. Both whole-cell S. typhi and STF suppressed proliferation to PHA and TT. This decreased proliferation was not a result of increased Mphi production of nitric oxide, prostaglandin E2, or oxygen radicals or the release of interleukin-1beta , tumor necrosis factor alpha, interleukin-6, or interleukin-10 following exposure to STF. However, the ability to take up soluble antigen, as determined by fluorescein isothiocyanate-labeled dextran uptake, was reduced in cells cultured with STF. Moreover, there was a dramatic reduction in the expression of CD54 on Mphi after exposure to STF. These results indicate that whole-cell S. typhi and STF have the ability to alter in vitro proliferation to soluble antigens and mitogens by affecting Mphi function.

* Corresponding author. Mailing address: Center for Vaccine Development, Department of Pediatrics, University of Maryland, 685 W. Baltimore St., Rm. 480, Baltimore, MD 21201. Phone: (410) 706-5328. Fax: (410) 706-6205. E-mail: msztein{at}UMPPA1.ab.umd.edu.

Infection and Immunity, March 1999, p. 1338-1346, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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