Bacterial and viral infections and related inflammatory responses in chronic obstructive pulmonary disease

Abstract

In chronic obstructive pulmonary disease (COPD) patients, bacterial and viral infections play a relevant role in worsening lung function and, therefore, favour disease progression. The inflammatory response to lung infections may become a specific indication of the bacterial and viral infections. We here review data on the bacterial-viral infections and related airways and lung parenchyma inflammation in stable and exacerbated COPD, focussing our attention on the prevalent molecular pathways in these different clinical conditions. The roles of macrophages, autophagy and NETosis are also briefly discussed in the context of lung infections in COPD. Controlling their combined response may restore a balanced lung homeostasis, reducing the risk of lung function decline. KEY MESSAGE Bacteria and viruses can influence the responses of the innate and adaptive immune system in the lung of chronic obstructive pulmonary disease (COPD) patients. The relationship between viruses and bacterial colonization, and the consequences of the imbalance of these components can modulate the inflammatory state of the COPD lung. The complex actions involving immune trigger cells, which activate innate and cell-mediated inflammatory responses, could be responsible for the clinical consequences of irreversible airflow limitation, lung remodelling and emphysema in COPD patients.

Keywords: B cells; ILCs; NETosis; NK cells; T-lymphocytes; autoimmunity; autophagy; dendritic cells; disability; macrophages; outcome; pyroptosis.

Figure 1.

Schematic representation of the changes in microbiota and inflammation in COPD patients. Top, airway mucosa of healthy subjects presents a normal muco-microbiotic layer characterized by eubacteria. In contrast, in COPD patients, the muco-microbiotic layer is altered by pathogenic bacteria and viruses, which are associated with an inflammatory state of the bronchial-bronchiolar mucosa (epithelium and lamina propria). As a hypothesis, administration of probiotics may ameliorate the histopathological features of the airways, contributing to restoring a normal homeostasis in the lung. Bottom, the scheme shows that: (1) eubacteria have anti-inflammatory effects; (2) pathogenetic bacteria and viruses have pro-inflammatory effects; (3) eubacteria and pathogenic bacteria show antagonist actions; (4) pathogenic bacteria and viruses show agonist-challenging and pro-inflammatory actions.

Figure 2.

Schematic representation of necroptosis and pyroptosis cellular functions. In necroptosis, pro-inflammatory cytokines and/or LPS bind their own receptors on the cell membrane, which activate the necrosome complex. This, in turn, activates the MLKL complex damaging the cellular membrane, MLKL pore formation and release of DAMPS, K⁺ and IL-1β. In the pyroptosis “canonical model”, DAMPS, toxins, ATP, uric-acid crystals or other cellular stressors activate the inflammasome complex, which can bind pro-caspase 1 involved in the activation of caspase-1 followed by activation of IL-1β and IL-18 that are released through gasdermin pores. In the “non-canonical” pyroptosis model, bacteria, viruses and other stressors bind procaspase 4/5/11, which, after activation, induces the production and release through gasdermin pores of DAMPS and proinflammatory cytokines such as IL-1β and IL-18. DAMPs: damage-associated molecular patterns; TLR: toll like receptor; GSDMD: gasdermin D; MLKL: mixed lineage kinase domain like pseudokinase; RIPK1-3: receptor-interacting protein kinase 1–3.

Figure 3.

Schematic representation of efferocytosis for apoptotic cells or bacteria. The phagocytized material is transported inside the cell cytoplasm and processed as phagosome. Then, it merges with one or more lysosomes to produce a phagolysosome complex, where the action of enzymes and ROS degrades phagocytized cells. Viral derived M2 protein may reduce the phagolysosome formation. At the end of the process, debris will be exocyted from the cell. The process is considered “immunologically silent” with a low level of pro-inflammatory cytokine production like IL-1 β, IL-12, IFN α/β. MARCO: macrophage receptor with collagenous structure; Stab2: stabilin receptor-2; RAGE: receptor for advanced glycation end products; RAC1: Ras-related C3 botulinum toxin substrate 1; Mer-TK: proto-oncogene tyrosine-protein kinase MER; ROS: reactive oxygen species; LC3 II: microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate.