Induction of adaptive immunity leads to the establishment of immunological memory; however, how innate immunity regulates memory T cell function remains obscure. Here we show a previously undefined mechanism in which innate and adaptive immunity are linked by TIR domain-containing adapter-inducing beta interferon (TRIF) during establishment and reactivation of memory T cells against Gram-negative enteropathogens. Absence of TRIF in macrophages (Mϕs) but not dendritic cells led to a predominant generation of CD4(+) central memory T cells that express IL-17 during enteric bacterial infection in mice. TRIF-dependent type I interferon (IFN) signaling in T cells was essential to Th1 lineage differentiation and reactivation of memory T cells. TRIF activated memory T cells to facilitate local neutrophil influx and enhance bacterial elimination. These results highlight the importance of TRIF as a mediator of the innate and adaptive immune interactions in achieving the protective properties of memory immunity against Gram-negative bacteria and suggest TRIF as a potential therapeutic target.
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