Virulent <i>Salmonella enterica</i> infections can be exacerbated by concomitant infection of the host with a live attenuated <i>S. enterica</i> vaccine via Toll‐like receptor 4‐dependent interleukin‐10 production with the involvement of both TRIF and MyD88

Summary During systemic disease in mice, Salmonella enterica grows intracellularly within discrete foci of infection in the spleen and liver. In concomitant infections, foci containing different S. enterica strains are spatially separated. We have investigated whether functional interactions between bacterial populations within the same host can occur despite the known spatial separation of the foci and independence of growth of salmonellae residing in different foci. In this study we have demonstrated that bacterial numbers of virulent S. enterica serovar Typhimurium C5 strain in mouse tissues can be increased by the presence of the attenuated aroA S. Typhimurium SL3261 vaccine strain in the same tissue. Disease exacerbation does not require simultaneous coinjection of the attenuated bacteria. SL3261 can be administered up to 48 hr after or 24 hr before the administration of C5 and still determine higher tissue numbers of the virulent bacteria. This indicates that intravenous administration of a S. enterica vaccine strain could potentially exacerbate an established infection with wild‐type bacteria. These data also suggest that the severity of an infection with a virulent S. enterica strain can be increased by the prior administration of a live attenuated vaccine strain if infection occurs within 48 hr of vaccination. Exacerbation of the growth of C5 requires Toll‐like receptor 4‐dependent interleukin‐10 production with the involvement of both Toll/interleukin‐1 receptor‐domain‐containing adaptor inducing interferon‐β and myeloid differentiation factor 88.