Neural pathways in allergic inflammation

Abstract

Allergy is on the rise worldwide. Asthma, food allergy, dermatitis, and systemic anaphylaxis are amongst the most common allergic diseases. The association between allergy and altered behavior patterns has long been recognized. The molecular and cellular pathways in the bidirectional interactions of nervous and immune systems are now starting to be elucidated. In this paper, we outline the consequences of allergic diseases, especially food allergy and asthma, on behavior and neural activity and on the neural modulation of allergic responses.

Figure 1

Early phase and late phase of allergic hypersensitivity. Upon allergen challenge, sensitized individuals can present two distinct phases: the early phase, which is characterized by mast cell degranulation and release of inflammatory mediators triggered by cross-linking IgE antibodies present on mast cells membranes, and the late phase, that is characterized by the infiltration of Th2 cells that interact with dendritic cells releasing type 2 cytokines responsible for tissue mast cell proliferation and eosinophil recruitment.

Figure 2

Activation of specific brain areas by c-fos expression. Representative brain coronal sections of nonallergic (nonsensitized) and allergic (OVA-sensitized) mice after (oral or nasal) challenge with OVA. Fos staining in neurons of (a) the paraventricular nucleus of the hypothalamus (PVN), (b) nucleus of the tract solitary (NTS), and (c) central nucleus of the amygdala (CeA). Adapted from Basso et al. 2004 [36] and Costa-Pinto et al. [47].

Figure 3

The cholinergic pathways in allergic lung. During allergic reactions, the inflammatory mediators released in the tissue activate the sensory afferent fibers, which convey information to the CNS. The CNS sends information back to the inflammatory site by increasing ACh release from efferent vagus nerve. The neurotransmission in the parasympathetic ganglia is mediated by acetylcholine (ACh) via nicotinic (nAChR) or type 1 muscarinic (m1AChR) receptors. The stimulus generated induces ACh release in the pos ganglionic nerve fiber endings. Type 2 muscarinic receptors (m2AChRs) are autoinhibitory, and the dysfunction of this receptor, observed in allergic asthma, induces increased release of ACh. Increased ACh results in augmented mucus secretion via m3AchR expressed in the glandular epithelium, increased airway smooth muscle contraction (bronchoconstriction) via m3AchR expressed in muscle cells, and decreased inflammatory mediators production via a7nAChR receptor expressed on immune cells.