ILC1 and TRM occupy the same mucosal barrier niche and provide non-overlapping protection against infection

Abstract

Abstract Tissue-resident memory T cells (TRM) occupy front-line niches in barrier tissues where they are poised to rapidly respond to secondary infection. Intriguingly, even though new infections result in new populations of TRM, there appears to be enough space in the tissue to accommodate new TRM without displacing older cells. We have recently been investigating how the oral mucosa is protected against infection using a newly developed model of viral infection of the inner lip with vaccinia virus (VACV). Many orthopoxviruses including variola (the causative agent of smallpox), are thought to have invaded through the oropharyngeal mucosa. We have previously shown that group 1 innate lymphoid cells (ILCs) are the major force protecting the oral mucosa during VACV infection. ILC1s serve as the primary source for IFN-γ, which is critical to restrict viral replication. In a tissue heavily populated with ILC1s, however, it is unclear what, if any, role other tissue resident memory cells (including TRM) play during infection. We have used a combination of static and intravital imaging of Rag−/− Il12rg−/− mice and Ncr1-gfp+ reporter mice to spatially map ILC1 and TRM locations in the oral mucosa. Using Rag−/−Il12rg−/− mice and Rag− /− T-bet-ZsGreen reporter mice and adoptive transfer of virus-specific T cells, we plan to examine the function of ILC1s and TRM in the absence of the other cell population as well as when both are present. We are further exploring whether competition for local cytokines could be regulating niche occupancy. Together, these data will expand our understanding on the complex interplay between innate and adaptive immune cells during viral infection of a critical but often overlooked barrier tissue.