Control of Persistent <i>Salmonella</i> Infection Relies on Constant Thymic Output Despite Increased Peripheral Antigen-Specific T Cell Immunity

• Main Authors: J. Alan Goggins, Jonathan R Kurtz, James B. McLachlan
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Pathogens
• Subjects: <i>Salmonella</i>; CD4⁺ helper T cells; thymus; IL-17; persistent infection; recent thymic emigrants
• Online Access: https://www.mdpi.com/2076-0817/9/8/605

Recent thymic emigrants are the youngest subset of peripheral T cells and their involvement in combating persistent bacterial infections has not been explored. Here, we hypothesized that CD4⁺ recent thymic emigrants are essential immune mediators during persistent <i>Salmonella</i> infection. To test this, we thymectomized adult mice either prior to, or during, persistent <i>Salmonella</i> infection. We found that thymic output is crucial in the formation of protective immune responses during the early formation of a <i>Salmonella</i> infection but is dispensable once persistent <i>Salmonella</i> infection is established. Further, we show that thymectomized mice demonstrate increased infection-associated mortality and bacterial burdens. Unexpectedly, numbers of <i>Salmonella</i>-specific CD4⁺ T cells were significantly increased in thymectomized mice compared to sham control mice. Lastly, we found that T cells from thymectomized mice may be impaired in producing the effector cytokine IL-17 at early time points of infection, compared to thymically intact mice. Together, these results imply a unique role for thymic output in the formation of immune responses against a persistent, enteric pathogen.