Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). However, initiation of adaptive immune responses is also controlled by regulatory T cells (TR cells), which act to prevent activation of autoreactive T cells. Here we describe a second mechanism of immune induction by TLRs, which is independent of effects on costimulation. Microbial induction of the Toll pathway blocked the suppressive effect of CD4+CD25+ TR cells, allowing activation of pathogen-specific adaptive immune responses. This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products.

Toll-like receptors (TLRs) detect microbial infection and have an essential role in the induction of immune responses. TLRs can directly induce innate host defence responses, but the mechanisms of TLR-mediated control of adaptive immunity are not fully understood. Although TLR-induced dendritic cell maturation is required for activation of T-helper (T(H)) cells, the role of TLRs in B-cell activation and antibody production in vivo is not yet known. Here we show that activation and differentiation of T(H) cells is not sufficient for the induction of T-dependent B-cell responses. We find that, in addition to CD4+ T-cell help, generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells.

Work in recent years has shown an essential role for Toll-like receptors (TLRs) in the activation of innate and adaptive immunity in vertebrate animals. These germ-line encoded receptors, expressed on a diverse variety of cells and tissues, recognize conserved molecular products derived from various classes of pathogens, including Gram-positive and -negative bacteria, DNA and RNA viruses, fungi and protozoa. Ligand recognition induces a conserved host defense program, which includes production of inflammatory cytokines, upregulation of costimulatory molecules, and induction of antimicrobial defenses. Importantly, activation of dendritic cells by TLR ligands is necessary for their maturation and consequent ability to initiate adaptive immune responses. How responses are tailored by individual TLRs to contain specific classes of pathogens is not yet clear.