Innate immunity and asthma

Abstract

Asthma remains a major health problem worldwide that has increased in developed countries. Much of the focus in asthma research in the past has been on adaptive, antigen-dependent immune responses. Recent work suggests that the innate, non-antigen-dependent immune system plays a critical role in asthma pathogenesis. Here we will highlight innate receptors and cells in the context of allergic responses. Reviewing animal models and human studies, we focus on interactions of innate and adaptive immunity.

Figure 1.

Adaptive immune responses. Antigen-presenting cells (APC) bind, process antigen (Ag), and display it on their surface on the major histocompatability complex (MHC). This is then able to bind an antigen-specific T cell receptor (TCR) on the surface of the naïve T cell (also known as signal 1). To respond to this antigen, the T cell must also be costimulated through additional receptors (costimulation, also known as signal 2). This dual stimulation can lead to a Thelper (Th)1 or Th2 response, depending on the antigen. The innate immune system plays a critical role in determining the type of T cell differentiation and, thus, the type of adaptive immune response. A newly described subset, Th17 cells, mediates neutrophil inflammation and may play a role in asthma.

Figure 2.

Toll-like receptors (TLRs), their ligands, and cellular location. TLR1, 2, 4, 5, and 6 are located on the plasma membrane, while TLR3, 7, 8, and 9 are located in intracellular compartments such as endosomes. Each TLR recognizes a discrete set of ligands and can form homo- or heterodimers, thus increasing the number of ligands recognized. Each TLR has a ligand-binding domain containing leucine-rich repeats. The cytoplasmic portion of the receptor contains a TIR domain that lacks signaling capability, but binds adaptor proteins when ligand is bound. dsRNA = double-stranded RNA; LPS = lippolysaccharide; ssRNA = single-stranded RNA; TIR = Toll-like and interleukin 1 receptor.

Figure 3.

Regulatory T cells (Tregs) and adaptive immunity. Tregs differentiate from naïve T cells in response to antigen, and this may be influenced by TLRs binding their cognate ligands on APCs or T cells. Tregs are IL-10 dependent and they secrete IL-10 that exerts a suppressive effect on Th1 and Th2 phenomena. Substantial data also indicate that transforming growth factor-β is secreted by regulatory T cells and that this cytokine has important regulatory effects. Ag = antigen; MHC = major histocompatability complex;TCR = T cell receptor; Th = T helper.