T cell-dependent and -independent IgA responses: role of TLR signalling.

Immunoglobulin A (IgA) represents the primary line of protection against incoming pathogens since it is the predominant isotype on mucosal surfaces. Mucosal surfaces are constantly exposed to inhaled, digested and sexually transmitted agents and therefore highly susceptible to infection by invading pathogens. Such pathogens typically carry pathogen-associated molecular patterns (PAMPs) which primarily signal through Toll-like receptors (TLRs). TLRs belong to a family of pattern-recognition receptors that link the innate and the acquired immune system. TLR stimulation in professional antigen-presenting cells (APCs) such as dendritic cells (DCs) is crucial for an optimal cellular and humoral immune response to be induced. Moreover TLRs have been shown to improve humoral responses by direct stimulation of B cells. Herein we review recent data, which points to a pivotal role of TLR signalling in controlling T-cell dependent and independent IgA responses both at mucosal and systemic levels. A better understanding of these mechanisms may facilitate the use of TLR agonists as adjuvants and consequently improve the development of effective mucosal vaccines.