According to conventional wisdom, pathogenic gut bacteria spread to distant tissues via an orderly march from gut to local lymph nodes (LNs) and then on to distant organs. But some mutant bugs that cannot invade the lymphoid tissues of the gut can still spread, hinting at the existence of an alternative route.
Barnes and colleagues infected mice orally with Yersinia pseudotuberculosis. They noted two waves of bacteria that spread to both the spleen and liver in the infected mice. The first wave occurred within 30 minutes of infection and was rapidly cleared from these distant organs. The second began later and stuck around.
Only the second wave of bacteria side-stepped the LNs, as mice lacking Peyer's patches—the gut lymphoid tissue that bacteria traverse to reach the LNs—developed only late-stage infections in the liver and spleen.
Marking individual bacteria with unique oligonucleotide tags revealed that the bugs entrenched in distant organs were descendants only of those that migrated later, after first replicating in the gut—possibly because replication triggers the expression of virulence factors that protect the bug against the host immune response.
How the disseminating bugs bypass the LNs remains to be determined. Perhaps they piggy-back on dendritic cells, which can reach directly across the gut epithelium to grab antigens and then head straight for the circulation.