The upper airways of the respiratory tract are relatively rich in microbes. Sampling of the lower airways of the lung have shown that there is a much lower biomass and much fewer microbes present. However, the lower airways are not sterile and have a considerable diversity of microbes. These microbes collectively form an ecological community that share this space, called a microbiome. This microbiome consist of symbiotic and commensal microbes that support the healthy lung but can also include pathogenic microbes that can contribute to lung and other diseases.

^{Normal lung microbiome created by Sarah Perkins under a CC BY NC ND license.}  

Microbiome of the Lung

Throughout the 1900s it was widely believed that the lung was a sterile space where microbes could not grow. Modern techniques involving DNA sequencing-based microbe identification have since revealed that the microbiome is an important part of a healthy lung and that microbes may protect the lung from injury and the development of allergies. The resident microbes of the lung exist in a natural balance and are part of lung homeostasis. During infection, these microbes may communicate with and alert our immune system to increase mucus secretion and other host defenses. Chronic lung disease disrupt the microbial balance and may leave the lung more susceptible to infection.

Lung Epithelium as a Barrier to Infection

A person will breath 10,000L of air each day and this this air will contact lung epithelium that spans a vast surface area (over 100 m²) in order to enable efficient gas exchange. Tightly packed epithelium cells are needed to keep microbes from entering human tissues. In the airways, these cells secrete an additional protective layer of mucus, while the alveoli are protected by secretion of surfactant. It is important to note that the walls of the alveoli are very thin to allow for efficient gas exchange.  When pathogens penetrate this thin alveolar wall, the tissue becomes inflamed and immune cells enter into the alveolar sac as pus. This immune reponse to infection is pneumonia.

Mucociliary Clearance

The trachea, bronchi and larger bronchioles contain mucus-producing goblet cells and submucosal glands. The airway is also lined with epithelial cells that have hair-like projections called cilia, which work in conjunction to goblet cells in order to maintain a nearly sterile lung through the process of mucociliary clearance. Mucus is a sticky and viscous substance that often contains antimicrobial components, such as lysozyme enzyme or immunoglubulin A (IgA). Small particulate dust or pollutants, allergens, infectious agents become trapped in the viscous mucus. The movement of cilia on the surface of airway epithelia carries mucus-encapsulated particles away from the respiratory zone of the lung .

Barriers to Alveolar Infection

Throughout the respiratory tract, the airway lumen is lined with epithelial cells that associate by tight junctions to prevent infection. Mucus also serves as a physical barrier and a carrier for mucociliary clearance. However, the mucociliary system does not extend to the alveoli because mucus impedes airflow and gas exchange. Instead, alveolar cells consist of type I pneumocytes, which are optimized for gas exchange, and type II pneumocytes, which are more numerous and perform secretory functions.

Alveolar pneumocytes still form epithelial tight junctions, but unlike the thicker pseudostratified cell layers of the bronchi, the alveolar cells form a squamous thin layer of cells. Type II pneumocytes secrete surfactant to primarily reduce surface tension and prevent alveolar collapse. However, surfactant also contains proteins that opsonize foreign cells, making them more likely to be consumed by phagocytes.

Immune cells, such as macrophages and dendritic cells, play an important role in removing debris and infectious agents within the alveoli. Macrophages and dendritic cells are phagocytes, meaning that they consume foreign material. These cells may remain within the epithelium or enter the air spaces to eliminate infectious agents, toxins, or allergens. In the context of an infection, these cells are potent inducers of inflammation and in persistent infection they alert the T-cells and B-cells of the adaptive immune response, through a process called antigen presentation.

Section Review

• The upper respiratory tract is typically colonized by commensal microbes, collectively known as the microbiome.
• The lower respiratory tract, including the lungs, have a microbiome consisting of significantly fewer microbes.
• The microbe-poor alveoli of the lung are maintained by preventing microbes from reaching the alveoli via mucus secretion and ciliary clearance of the mucus-encapsulated microbes in the upper airway.
• Surfactant secretion as well as resident macrophage immune cells are barriers to infection in the alveoli.
• Macrophages can also trigger inflammation that is characteristic of pneumonia.

Review Questions