Chemokine expression heightens antibacterial immunity

September 12, 2001

Macrophage-derived chemokine (MDC) acts preferentially on Th2 lymphocytes, promoting their migration and setting the stage for antigen-specific B cell responses. Although this chemokine is expressed at low constitutive levels in antigen-presenting cells, Kikuchi and Crystal hypothesized that increasing its expression in dendritic cells (DCs) could allow for more efficient T cell help and a more effective humoral response. Since antibodies are key to the suppression of bacterial infections, these authors tested their idea in a mouse model of bacterial pneumonia. They transduced DCs with a human MDC cDNA and exposed the transgenic cells to pathogenic Pseudomonas bacteria, allowing the cells to process and display bacterial antigens. When reintroduced into host mice, these antigen-pulsed DCs effectively suppressed otherwise lethal infections with Pseudomonas. As expected, passive transfer of CD4 cells that had been activated by these DCs conferred the same protection to naive hosts, and even simple transfer of the serum from DC recipient animals allowed otherwise untreated recipients to combat the infection. Control DCs that were exposed to the pathogen but that express only endogenous, low levels of MDC conferred only minimal protection to recipient animals. This approach allows for specific immunization against this one pathogenic species, but it is fully effective only against certain clinical isolates. Hence if this approach is to be tried for clinical purposes, it may be necessary to expose DCs to multiple bacterial strains. Kikuchi and Crystal also note that increased MDC expression by DCs could promote undesired Th2-dependent immune responses, such as those associated with allergic symptoms.
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