Current insights into the biology and pathogenesis of Pneumocystis pneumonia

Abstract

The fungal infection Pneumocystis pneumonia is the most prevalent opportunistic infection in patients with AIDS. Although the analysis of this opportunistic fungal pathogen has been hindered by the inability to isolate it in pure culture, the use of molecular techniques and genomic analysis have brought insights into its complex cell biology. Analysis of the intricate relationship between Pneumocystis and the host lung during infection has revealed that the attachment of Pneumocystis to the alveolar epithelium promotes the transition of the organism from the trophic to the cyst form. It also revealed that Pneumocystis infection elicits the production of inflammatory mediators, culminating in lung injury and impaired gas exchange. Here we discuss these and other recent findings relating to the biology and pathogenesis of this intractable fungus.

Pneumocystis jirovecii Pneumonia in AIDS Patients

“…However, studies of cultured lung epithelial cells have shown that the adherence of Pneumocystis alone does not disrupt the structure or barrier function of alveolar epithelial cells, although proliferative repair of the epithelium is reduced. It is therefore unlikely that the adherence of Pneumocystis to alveolar epithelium is by itself responsible for the diffuse alveolar damage in severe pneumonia (Benfield et al, 1997;Thomas & Limper, 2007). Rather, the inflammatory responses in the host are primarily responsible for the compromise of the alveolar-capillary surface (Thomas & Limper, 2007).…”

“…In contrast, surfactant protein D mediates the aggregation of the Pneumocystis organisms, but because the aggregated organisms are extremely poorly taken up by macrophages, they may escape elimination. Pulmonary surfactant phospholipids, which contribute to the low surface tension in the alveoli, are reduced during PcP, and abnormalities in the composition and function of the surfactant are the result of the host's inflammatory response to Pneumocystis, rather than direct effects of the organisms on the surfactant components (Wright et al, 2001;Thomas & Limper, 2007).…”

“…Other laboratory diagnostic methods 7.3.1 Beta-D-glucan assay -1,3-glucan (BG) is the main structural component of the cell wall of all fungi, including Pneumocystis cysts (Thomas & Limper, 2007). Interestingly, high serum BG levels have been reported in patients with PcP (Desmet et al, 2009;Nakamura et al, 2009;Teramoto et al, 2000).…”

“…It is therefore unlikely that the adherence of Pneumocystis to alveolar epithelium is by itself responsible for the diffuse alveolar damage in severe pneumonia (Benfield et al, 1997;Thomas & Limper, 2007). Rather, the inflammatory responses in the host are primarily responsible for the compromise of the alveolar-capillary surface (Thomas & Limper, 2007). Electron microscopic studies have shown that Pneumocystis organisms are embedded in protein-rich alveolar exudates, which contain abundant fibronectin, vitronectin, and hydrophilic surfactant proteins A and D. In contrast, hydrophobic surfactant protein B and C are reduced during PcP.…”

Pneumocystis pneumonia: immunosuppression, Pneumocystis jirovecii...and the third man

“…The Review article by Thomas and Limper on Pneumocystis pneumonia (PcP) published in Nature Reviews Microbiology illustrates the biological insights that have been gained from the use of molecular tools and the more recent technique of observation 1 . In this Correspondence, we discuss recent findings concerning the prevalence of trichomonads in the lungs of patients in different clinical contexts, including PcP.…”