Expression of <i>E. coli</i> FimH Enhances Trafficking of an Orally Delivered <i>Lactobacillus acidophilus</i> Vaccine to Immune Inductive Sites via Antigen-Presenting Cells
The development of lactic acid bacteria as mucosal vaccine vectors requires the identification of robust mucosal adjuvants to increase vaccine effectiveness. The <i>E. coli</i> type I fimbriae adhesion protein FimH is of interest as a mucosal adjuvant as it targets microfold (M) cells en...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/11/7/1162 |
| Summary: | The development of lactic acid bacteria as mucosal vaccine vectors requires the identification of robust mucosal adjuvants to increase vaccine effectiveness. The <i>E. coli</i> type I fimbriae adhesion protein FimH is of interest as a mucosal adjuvant as it targets microfold (M) cells enhancing vaccine uptake into Peyer’s patches and can activate the innate immune system via Toll-like receptor (TLR) 4 binding. Here, we displayed the N-terminal domain of FimH on the surface of a <i>Lactobacillus acidophilus</i> vaccine vector and evaluated its ability to increase uptake of <i>L. acidophilus</i> into Peyer’s patches and activate innate immune responses. FimH was robustly displayed on the <i>L. acidophilus</i> surface but did not increase uptake into the Peyer’s patches. FimH did increase trafficking of <i>L. acidophilus</i> to mesenteric lymph nodes by antigen-presenting cells including macrophages and dendritic cells. It also increased transcription of retinaldehyde dehydrogenase and decreased transcription of IL-21 in the Peyer’s patches and mesenteric lymph nodes. The N-terminal domain of FimH did not activate TLR4 in vitro, indicating that FimH may stimulate innate immune responses through a not-yet-identified mechanism. These results indicate that <i>E. coli</i> FimH alters the innate immune response to <i>L. acidophilus</i> and should be further studied as an adjuvant for lactic acid bacterial vaccine platforms. |
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| ISSN: | 2076-393X |