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Infection and Immunity, November 2008, p. 5191-5199, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00759-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity{triangledown}

Douglas M. Heithoff,1,{dagger} Elena Y. Enioutina,2,{dagger} Diana Bareyan,2 Raymond A. Daynes,2 and Michael J. Mahan1*

Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106,1 Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 841322

Received 17 June 2008/ Returned for modification 7 August 2008/ Accepted 21 August 2008

Immunity conferred by conventional vaccines is restricted to a narrow range of closely related strains, highlighting the unmet medical need for the development of vaccines that elicit protection against multiple pathogenic serotypes. Here we show that a Salmonella bivalent vaccine comprised of strains that lack and overproduce DNA adenine methylase (Dam) conferred cross-protective immunity to salmonella clinical isolates of human and animal origin. Protective immunity directly correlated with increased levels of cross-reactive opsonizing antibodies and memory T cells and a diminished expansion of myeloid-derived suppressor cells (MDSCs) that are responsible for the immune suppression linked to several conditions of host stress, including chronic microbial infections, traumatic insults, and many forms of cancer. Further, aged mice contained increased numbers of MDSCs and were more susceptible to Salmonella infection than young mice, suggesting a role for these cells in the immune declines associated with the natural aging process. These data suggest that interventions capable of reducing MDSC presence and activities may allow corresponding increases in B- and T-cell stimulation and benefit the ability of immunologically diverse populations to be effectively vaccinated as well as reducing the risk of susceptible individuals to infectious disease.

* Corresponding author. Mailing address: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106. Phone: (805) 893-7160. Fax: (805) 893-4724. E-mail: mahan{at}lifesci.lscf.ucsb.edu

{triangledown} Published ahead of print on 2 September 2008.

Editor: J. B. Bliska

{dagger} D.M.H. and E.Y.E. contributed equally to this work.

Infection and Immunity, November 2008, p. 5191-5199, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00759-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hanson, E. M., Clements, V. K., Sinha, P., Ilkovitch, D., Ostrand-Rosenberg, S. (2009). Myeloid-Derived Suppressor Cells Down-Regulate L-Selectin Expression on CD4+ and CD8+ T Cells. J. Immunol. 183: 937-944 [Abstract] [Full Text]  


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