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Infection and Immunity, March 2004, p. 1450-1462, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1450-1462.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Bordetella pertussis Infection of Primary Human Monocytes Alters HLA-DR Expression

Jennifer A. Shumilla,1,{dagger} Vashti Lacaille,1,{ddagger} Tara M. C. Hornell,1 Jennifer Huang,1 Supraja Narasimhan,1 David A. Relman,2,3* and Elizabeth D. Mellins1*

Department of Pediatrics,1 Departments of Microbiology and Immunology and Medicine, Stanford University School of Medicine, Stanford,2 Veterans Affairs Palo Alto Health Care System, Palo Alto, California3

Received 16 September 2003/ Returned for modification 23 October 2003/ Accepted 5 November 2003

Bordetella pertussis is the causative agent of whooping cough, a potentially lethal respiratory disease in children. In immunocompetent individuals, B. pertussis infection elicits an effective adaptive immune response driven by activated CD4+ T cells. However, live B. pertussis persists in the host for 3 to 4 weeks prior to clearance. Thus, B. pertussis appears to have evolved short-term mechanisms for immune system evasion. We investigated the effects of B. pertussis wild-type strain BP338 on antigen presentation in primary human monocytes. BP338 infection reduced cell surface expression of HLA-DR and CD86 but not that of major histocompatibility complex class I proteins. This change in cell surface HLA-DR expression reflected intracellular redistribution of HLA-DR. The proportion of peptide-loaded molecules was unchanged in infected cells, suggesting that intracellular retention occurred after peptide loading. Although B. pertussis infection of monocytes induced rapid and robust expression of interleukin-10 (IL-10), HLA-DR redistribution did not appear to be explained by increased IL-10 levels. BP338-infected monocytes exhibited reduced synthesis of HLA-DR dimers. Interestingly, those HLA-DR proteins that were generated appeared to be longer-lived than HLA-DR in uninfected monocytes. BP338 infection also prevented gamma interferon (IFN-{gamma}) induction of HLA-DR protein synthesis. Using mutant strains of B. pertussis, we found that reduction in HLA-DR surface expression was due in part to the presence of pertussis toxin whereas the inhibition of IFN-{gamma} induction of HLA-DR could not be linked to any of the virulence factors tested. These data demonstrate that B. pertussis utilizes several mechanisms to modulate HLA-DR expression.

* Corresponding author. Mailing address for E. D. Mellins: Department of Pediatrics, Stanford University School of Medicine, 269 Campus Dr., CCSR Building 2115c, Stanford, CA 94305. Phone: (650) 498-7350. Fax: (650) 736-0194. E-mail: mellins{at}stanford.edu. Mailing address for D. A. Relman: Department of Medicine, Stanford University School of Medicine, VA Palo Alto Health Care System 154T, Building 101, Room B4-18S, 3801 Miranda Ave., Palo Alto, CA 94304. Phone: (650) 852-3308. Fax: (650) 852-3291. E-mail: relman{at}stanford.edu.

Editor: J. N. Weiser

{dagger} Present address: Avigen, Inc., Alameda, CA 94502.

{ddagger} Present address: DiscoveRx Corporation, Fremont, CA 94538.

Infection and Immunity, March 2004, p. 1450-1462, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1450-1462.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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