Infection-Associated Mechanisms of Neuro-Inflammation and Neuro-Immune Crosstalk in Chronic Respiratory Diseases

Abstract

Chronic obstructive airway diseases are characterized by airflow obstruction and airflow limitation as well as chronic airway inflammation. Especially bronchial asthma and chronic obstructive pulmonary disease (COPD) cause considerable morbidity and mortality worldwide, can be difficult to treat, and ultimately lack cures. While there are substantial knowledge gaps with respect to disease pathophysiology, our awareness of the role of neurological and neuro-immunological processes in the development of symptoms, the progression, and the outcome of these chronic obstructive respiratory diseases, is growing. Likewise, the role of pathogenic and colonizing microorganisms of the respiratory tract in the development and manifestation of asthma and COPD is increasingly appreciated. However, their role remains poorly understood with respect to the underlying mechanisms. Common bacteria and viruses causing respiratory infections and exacerbations of chronic obstructive respiratory diseases have also been implicated to affect the local neuro-immune crosstalk. In this review, we provide an overview of previously described neuro-immune interactions in asthma, COPD, and respiratory infections that support the hypothesis of a neuro-immunological component in the interplay between chronic obstructive respiratory diseases, respiratory infections, and respiratory microbial colonization.

Adhesion Promotes Allergic Rhinitis CD4+IL4+ T Cell Differentiation via ICAM1 and E-Selectin

“…2 It has been reported that sensory nerves directly upregulat ILC2s activation by releasing of neuromedium U (NMU) in bronchial asthma, chronic obstructive pulmonary disease, and sepsis. 25,26 An α7 nicotinic acetylcholine receptor agonist inhibits ILC2-driven airway inflammation. 27 Substance P could induce CD301 + dendritic cell migration and further contribute to type 2 inflammation.…”

Neuroimmune Interaction: A Widespread Mutual Regulation and the Weapons for Barrier Organs

“…Sensory innervation of the respiratory tract mainly comes from the vagus branch from nodose/jugular ganglia and the somatosensory afferent nerves comes from neurons in the dorsal root ganglion ( Camp et al, 2021 ). Pulmonary sensory nerve endings express Toll-like receptors (TLRs, a type of pattern-dependent recognition receptor) that recognize pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharides (LPS, a component of the cell wall of gram-negative bacteria), and transmit signals to the central nervous system (CNS).…”

“…In the case of Staphylococcus aureus , SP stimulates bacterial virulence and promotes the migration, adhesion, and phagocytic activity of neutrophils. TRPV1+ afferent nerve in nociceptor modulates protective immunity by releasing cGRP, inhibiting neutrophil recruitment and γδT cell-mediated defense ( Baral et al, 2018 ; Camp et al, 2021 ). In helminth infection, NEB can release NMU and NMB to bidirectionally regulate the immune response.…”

“…SP increases adherent aggregation and phagocytic activity of neutrophils. VIP reduces the contraction response of airway smooth muscle and reduces the degree of airflow restriction ( Table 3 ) ( Camp et al, 2021 ).…”

“…SP promotes the degranulation of MCs, release of pro-inflammatory cytokines, and immune migration, increasing the adhesion of neutrophils to bronchial epithelial cells and neutrophils phagocytic activity. In addition, CGRP directly activates ILC2s at a close spatial distance under allergen stimulation, not only triggering downstream type 2 immune response but also promoting ILC2s to produce IL-5, recruiting eosinophils, and aggravating allergic reactions ( Camp et al, 2021 ). PNECs amplify inflammation by releasing CGRP and the neurotransmitter GABA.…”