Table 1.

Some knowledge gaps in understanding how TLRs regulate adaptive immunity

The role of TLRs in regulating the induction and maintenance of CD4+ and CD8+ T cell memory responses

The role of TLRs in regulating the induction and maintenance of the germinal center response, affinity maturation and generation of long lived antibody forming cells

How signals from multiple TLRs are integrated and the consequence for adaptive immunity

How signals from TLRs are integrated with signals from CLRs, NLRs, and RLRs, and the consequence for adaptive immunity

Organ-specific differences in TLR signaling (e.g. spleen versus intestines versus lung versus liver)

The mechanisms by which constitutive TLR signaling in the intestine are restrained from promoting overt inflammation and autoimmunity

The role of TLRs in regulating immunity to chronic infections. (i.e. the consequences of persistent TLR signaling by persistent chronic infections).