Immunopathogenesis of Staphylococcus aureus pulmonary infection

Abstract

Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia.

Fig. 1

Pathology of USA300 lung infections. H&E sections of C57Bl6/J mouse lung. Mice were infected with 2×10⁷ cfu S. aureus USA300 for 24 h. In the uninfected lung, two bronchioles and a blood vessel are visible, along with clear alveolar architecture. The USA300-infected animal shows loss of alveolar architecture, necrosis, hemorrhage, infiltration of immune cells, and consolidation of the lung parenchyma. Scale bars, 100 μm

Fig. 2

Virulence factors and host signaling cascades activated by S. aureus in the airway epithelium. Depicted are some of the virulence factors mentioned in the text and their effects on the host epithelium. See text for details

Fig. 3

S. aureus interactions with neutrophils and monocytes. S. aureus is able to persist intracellularly in neutrophils for days; their escape from vacuole compartments is reliant upon exotoxin production. Both PVL and PSMs have shown an ability to lyse neutrophils. In monocytes, interaction with S. aureus and the action of α-hemolysin lead to the activation of the inflammasome

Fig. 4

Iron-dependent regulation of virulence by Fur. In the presence of iron, Fur is able to increase the expression of iron transport systems (Hts, Isd) and the complement evasion proteins CHIPS and SCIN while decreasing exotoxin production. Other proteins known to aid in complement evasion are also shown

Fig. 5

S. aureus superantigens. S. aureus superantigens cause T cell proliferation, cytokine production, and apoptosis by simultaneously cross-linking MHCII molecules on antigen presenting cells with T cell receptors