Bordetella pertussisInfection of Primary Human Monocytes Alters HLA-DR Expression

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Abstract
Bordetella pertussisis the causative agent of whooping cough, a potentially lethal respiratory disease in children. In immunocompetent individuals,B. pertussisinfection elicits an effective adaptive immune response driven by activated CD4+T cells. However, liveB. pertussispersists in the host for 3 to 4 weeks prior to clearance. Thus,B. pertussisappears to have evolved short-term mechanisms for immune system evasion. We investigated the effects ofB. pertussiswild-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. AlthoughB. pertussisinfection 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-γ) induction of HLA-DR protein synthesis. Using mutant strains ofB. 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-γ induction of HLA-DR could not be linked to any of the virulence factors tested. These data demonstrate thatB. pertussisutilizes several mechanisms to modulate HLA-DR expression.

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