22.1 Anatomy and Normal Microbiota of the Respiratory Tract

The respiratory system is a complex network of structures that work together to facilitate breathing and protect against harmful microbes. From the nasal cavity to the alveoli, each part plays a crucial role in maintaining respiratory health and defending against pathogens.

Our respiratory tract is home to diverse microbial communities that interact with our immune system. While some microbes are beneficial, others can cause infections. Understanding these interactions is key to preventing and treating respiratory diseases.

Anatomy and Microbiota of the Respiratory Tract

Anatomical structures of respiratory tract

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• Upper respiratory tract consists of nasal cavity, pharynx, and larynx
  • Nasal cavity divided into nasal vestibule (anterior portion) and respiratory region (posterior portion) lined with ciliated epithelium and mucus-secreting goblet cells
  • Pharynx has three regions: nasopharynx (behind nasal cavity), oropharynx (behind oral cavity), and laryngopharynx (connects to esophagus and larynx)
  • Larynx contains vocal cords and epiglottis which prevents aspiration of food or liquid into the lower respiratory tract
• Lower respiratory tract includes trachea, bronchi, bronchioles, and alveoli
  • Trachea (windpipe) is a cartilage-reinforced tube that bifurcates into right and left primary bronchi
  • Bronchi branch into smaller secondary and tertiary bronchi, which further divide into bronchioles
  • Terminal bronchioles are the smallest airways without alveoli, while respiratory bronchioles have some alveoli budding off their walls
  • Alveoli are tiny air sacs arranged in clusters (alveolar sacs) where gas exchange occurs between the lungs and bloodstream
    • Pulmonary surfactant reduces surface tension in alveoli, preventing collapse during exhalation

Microbiota in respiratory regions

• Nasal cavity harbors skin-associated bacteria such as Staphylococcus spp. (S. aureus, S. epidermidis), Corynebacterium spp., and Propionibacterium spp. (P. acnes)
• Nasopharynx contains potential pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis that can cause upper respiratory infections (otitis media, sinusitis)
• Oropharynx has a diverse microbiota including Streptococcus spp. (S. salivarius, S. mitis), Neisseria spp., and the fungus Candida albicans
• Lower respiratory tract was traditionally thought to be sterile, but recent studies using molecular techniques suggest the presence of a lung microbiome
  • Predominant genera in the lung microbiome include Prevotella spp., Veillonella spp., and Streptococcus spp.
  • Composition of the lung microbiome can be altered in respiratory diseases (COPD, asthma, cystic fibrosis)

Respiratory tract defense mechanisms

• Mechanical defenses:
  1. Mucociliary escalator traps inhaled particles and microbes in mucus
  2. Coordinated beating of cilia sweeps mucus towards the pharynx to be swallowed or expectorated
  3. Epiglottic reflexes prevent microbes from entering the lower respiratory tract during swallowing or vomiting
• Innate immune defenses include antimicrobial peptides (defensins) in respiratory secretions, alveolar macrophages that phagocytose microbes, and neutrophils recruited during inflammation
  • Innate lymphoid cells contribute to mucosal immunity by producing cytokines and mediating tissue repair
• Adaptive immune defenses involve secretory IgA antibodies that neutralize microbes and toxins, as well as T cell and B cell-mediated specific immune responses
• Respiratory epithelium acts as a physical barrier and produces mucus, antimicrobial peptides, and inflammatory mediators

Pathogen bypass of respiratory defenses

• Pathogens employ various strategies to evade these defenses
  • Adherence to respiratory epithelial cells via adhesins or pili
  • Secretion of toxins that damage epithelial cells and impair ciliary function
  • Resistance to phagocytosis by alveolar macrophages and intracellular killing mechanisms
  • Antigenic variation of surface structures to evade antibody recognition

Microbe-respiratory system interactions

• Beneficial interactions:
  • Normal microbiota competes with pathogens for nutrients and attachment sites, preventing their overgrowth (colonization resistance)
  • Commensal microbes stimulate the development and regulation of the respiratory immune system
• Pathogenic interactions:
  • Viral infections cause upper respiratory illnesses (rhinovirus, influenza) and lower respiratory infections in children (RSV)
  • Bacterial pathogens cause pneumonia (S. pneumoniae), tuberculosis (M. tuberculosis), and whooping cough (B. pertussis)
  • Fungal infections like aspergillosis (A. fumigatus) and pneumocystis pneumonia (P. jirovecii) affect immunocompromised individuals
• Microbiome dysbiosis is associated with chronic respiratory diseases
  • COPD patients have increased Haemophilus spp. and decreased diversity in their lung microbiome
  • Asthma patients display an altered microbiome with increased Proteobacteria and decreased Bacteroidetes
  • Cystic fibrosis lungs are colonized by antibiotic-resistant Pseudomonas aeruginosa and other opportunistic pathogens