Induction of memory immunity to Mycobacterium tuberculosis is independent of Toll-like receptor 9 signaling (IRC9P.706)

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Abstract Mycobacterium tuberculosis (Mtb) is known to engage Toll-like receptors (TLR) 2 and 9 on macrophages and dendritic cells to initiate an inflammatory response. Nonetheless, studies in the murine model of tuberculosis revealed minimal involvement of TLR2 and TLR9 in host resistance during acute infection. We have published that the induction of memory immunity to Mtb is not compromised in the absence of TLR2. Given that the inclusion of TLR9 ligands in vaccine preparations enhances their efficacy, we hypothesized that TLR9 adjuvanticity is necessary for the induction of memory immunity to Mtb. Mice were immunized with an Mtb auxotroph. Upon challenge with Mtb, WT and TLR9-/- immunized mice demonstrated similarly enhanced control of bacterial burden in the lungs compared to their unimmunized counterparts. The granulomatous response, IFN-gamma production and the frequency of immune cells recruited to the lungs was similar in the two genotypes. These findings indicate that the absence of TLR9 signaling during priming does not affect T cell memory response to Mtb infection. Together, our studies point that induction of effector and memory T cell responses and resistance to acute Mtb infection are independent of TLR2 and TLR9. In a recent study we showed that TLR2 signaling, although nonessential in acute infection, was critical to host resistance during chronic Mtb infection. In ongoing studies we are investigating whether TLR9, like TLR2, has a role in chronic Mtb infection.