Salmonella sneaks past security

Certain gut cells can leave resident bacteria alone but respond selectively to invaders. Satoshi Uematsu, Shizuo Akira, and colleagues (Osaka University, Japan) suggest that gut cells achieve this differentiation by using a special, pathogen-specific receptor called the Toll-like receptor 5 (TLR5). But the pathogenic Salmonella typhimurium turns the situation around: events triggered by the special receptor help the bug to invade its host.

TLRs, which are expressed on professional antigen-presenting cells, recognize common pathogen-associated molecules and trigger innate immunity. TLR5 on dendritic cells recognizes bacterial flagellin protein in vitro, but its function in vivo was previously unknown.

Akira's team found that TLR5 mRNA was highly expressed in the mouse intestine particularly in a specific subpopulation of antigen-presenting lamina propria cells (CD11c⁺ LPCs). In these cells, TLR5 was necessary for bacterial flagellin to induce inflammatory cytokines, yet when the team infected TLR5^−/− mice with Salmonella, a flagellated bacterium, these mice were unexpectedly resistant to the bug.

It was not, however, invasion of the CD11c⁺ LPCs that showed a difference. In the gut, Salmonella invaded the CD11c⁺ LPCs in both TLR5^+/+ and TLR5^−/− mice. However, in the TLR5^−/− mice, fewer bacteria-laden CD11c⁺ LPCs moved from the intestinal tract to the mesenteric lymph nodes, probably because the LPCs failed to be activated by the bacteria. These mice had more resistance to systemic infection—fewer bacteria reached their livers and spleens—but it is not yet clear whether a similar tactic of TLR5 blocking would work in humans.

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