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.

Keywords: COPD; Staphylococcus aureus; asthma; influenza A virus; neuro-immune interactions; neuro-inflammation; neuropeptides; respiratory syncytial virus; rhinovirus.

Figure 1

Proposed interactions between chronic respiratory diseases and respiratory pathogens along the neuro-immune axis. Schematic illustration of a proposed neuro-immunological network including cells and mediators of the neuronal and immune system that contribute to the interplay between chronic respiratory diseases and respiratory infections by direct and indirect interaction. COPD = chronic obstructive pulmonary disease, PNECs = pulmonary neuroendocrine cells, IL = interleukin, IFN = interferon, SP = substance P, VIP = vasoactive intestinal peptide, CGRP = calcitonin gene related peptide, NMU = neuromedin U, ILC2s = group 2 innate lymphoid cells, NAMs = nerve- and airway associated macrophages, TH2 = T helper type 2. Created with BioRender.com.