Recent Advances in the Epidemiology and Pathogenesis of Pneumocystis Infection

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Fungal Pathogens".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 9103

Special Issue Editors


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Guest Editor
Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA Department of Thoracic Disease Research Unit, Mayo Clinic, Rochester, Minnesota, USA.
Interests: Fungal immunity; Pneumocystis; innate immunity; lung infections; chronic lung disease

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Guest Editor
Servicio de Medicina Interna, Instituto de Biomedicina de Sevilla (IBiS), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Hospital Universitario Virgen del Rocío, Seville, Spain. Departamento de Medicina, Universidad de Sevilla, Seville, Spain
Interests: Pneumocystis; infectious diseases; chronic lung diseases; epidemiology; infectious diseases immunity
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Special Issue Information

Dear Colleagues:

Pneumocystis jirovecii is an atypical fungus that exhibits high pulmonary tropism and specificity for the human host. Recent studies have begun to change the post-AIDS epidemic misconception that Pneumocystis pneumonia (PcP) was an infrequent disease and show that PcP remains a major opportunistic infection among HIV-infected patients and an emerging problem in non-HIV immunocompromised patients worldwide. In developed countries, the increase in PcP corresponds mainly with non-HIV patients, not only among those with transplant or cancer but also in subjects with underlying chronic lung diseases suggesting that PcP infection remains a public health problem with emerging new players.

In developing countries, a limited number of epidemiological studies have evaluated PcP prevalence and described an increased rate of infections in Africa, Asia and South America.

Besides Pneumocystis infection, colonization has been demonstrated not only in HIV-infected and non-HIV-infected immunosuppressed adults, but also in patients with chronic lung diseases. These groups are likely to represent a major reservoir of infection and further underline the need for increased efforts towards a better characterization of emerging risk groups and areas to improve prophylactic strategies to reduce disease burden.

One of the main challenges of studying pneumocystis is the inability to culture the organism. In recent years due to the rapid development of molecular tools, much has been learned about the epidemiology and biology of this challenging pathogen. However, the pathogenesis of the infection and new treatment options remains tremendously challenging areas where further investigations are needed.

In this Research Topic, we aim to provide a comprehensive up-to-date account on the status of relevant research in the field and highlight the potential of new tools and approaches to solve some longstanding issues regarding this opportunistic pathogen.

This Research Topic welcomes contributions in the form of Original Research and Review that focus on, but are not limited to, the following issues:

  • Epidemiology of PcP in developed and developing countries
  • Molecular epidemiology and modes of transmission of Pneumocystis infection
  • Genomics, transcriptomics and proteomics
  • Host-pathogen interactions, pathogenicity, and immunology
  • New findings related to drug discovery and treatment

Prof. Eva M. Carmona
Prof. F.J. Medrano
Guest Editors

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Keywords

  • Pneumocystis jirovecii
  • Pneumocystis pneumonia
  • epidemiology
  • molecular biology
  • immunology
  • pathogenesis

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Published Papers (2 papers)

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Review

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15 pages, 690 KiB  
Review
Pneumocystis Pneumonia: Immunity, Vaccines, and Treatments
by Aaron D. Gingerich, Karen A. Norris and Jarrod J. Mousa
Pathogens 2021, 10(2), 236; https://doi.org/10.3390/pathogens10020236 - 19 Feb 2021
Cited by 18 | Viewed by 5863
Abstract
For individuals who are immunocompromised, the opportunistic fungal pathogen Pneumocystis jirovecii is capable of causing life-threatening pneumonia as the causative agent of Pneumocystis pneumonia (PCP). PCP remains an acquired immunodeficiency disease (AIDS)-defining illness in the era of antiretroviral therapy. In addition, a rise [...] Read more.
For individuals who are immunocompromised, the opportunistic fungal pathogen Pneumocystis jirovecii is capable of causing life-threatening pneumonia as the causative agent of Pneumocystis pneumonia (PCP). PCP remains an acquired immunodeficiency disease (AIDS)-defining illness in the era of antiretroviral therapy. In addition, a rise in non-human immunodeficiency virus (HIV)-associated PCP has been observed due to increased usage of immunosuppressive and immunomodulating therapies. With the persistence of HIV-related PCP cases and associated morbidity and mortality, as well as difficult to diagnose non-HIV-related PCP cases, an improvement over current treatment and prevention standards is warranted. Current therapeutic strategies have primarily focused on the administration of trimethoprim-sulfamethoxazole, which is effective at disease prevention. However, current treatments are inadequate for treatment of PCP and prevention of PCP-related death, as evidenced by consistently high mortality rates for those hospitalized with PCP. There are no vaccines in clinical trials for the prevention of PCP, and significant obstacles exist that have slowed development, including host range specificity, and the inability to culture Pneumocystis spp. in vitro. In this review, we overview the immune response to Pneumocystis spp., and discuss current progress on novel vaccines and therapies currently in the preclinical and clinical pipeline. Full article
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9 pages, 1128 KiB  
Brief Report
Survey of the Transcription Factor Responses of Mouse Lung Alveolar Macrophages to Pneumocystis murina
by Theodore J. Kottom, Kyle Schaefbauer, Eva M. Carmona and Andrew H. Limper
Pathogens 2021, 10(5), 569; https://doi.org/10.3390/pathogens10050569 - 8 May 2021
Cited by 1 | Viewed by 2505
Abstract
Pneumocystis jirovecii is a fungal pathogen that can cause life-threatening infections in individuals who are immunocompromised. Acquired via inhalation, upon entering the respiratory tract, the fungi first encounter innate immune cells such as alveolar macrophages (AMs). Relatively little is known about the AM [...] Read more.
Pneumocystis jirovecii is a fungal pathogen that can cause life-threatening infections in individuals who are immunocompromised. Acquired via inhalation, upon entering the respiratory tract, the fungi first encounter innate immune cells such as alveolar macrophages (AMs). Relatively little is known about the AM cellular responses to the organism, and particularly transcription factor (TF) profiles leading to early host responses during infection. Utilizing the Mouse Transcription Factors RT2 Profiler™ PCR Array, we report an initial TF survey of these macrophage and Pneumocystis interactions. Expression levels of a panel of mouse TFs were compared between unstimulated and Pneumocystis murina-stimulated AMs. Interestingly, a number of TFs previously implicated in pathogen–host cell interactions were highly up- or downregulated, including hif1a and Pparg. qPCR experiments were further conducted to verify the results of these surveyed transcripts. Furthermore, with immunoblotting, we show that HIF-1A and PPAR-γ are indeed significantly upregulated and downregulated, respectively. Lastly, and importantly, we report that in the mouse model of Pneumocystis pneumonia (PCP), which mimics human Pneumocystis jirovecii pneumonia (PJP), qPCR analysis of Pneumocystis murina lungs also mimic the initial TF profile analysis, suggesting an importance for these TFs in immunocompromised hosts with Pneumocystis pneumonia. These data demonstrate the use of TF profiling in host AMs and Pneumocystis organism interactions that may lead to a better understanding of the specific inflammatory responses of the host to Pneumocystis pneumonia and may inform novel strategies for potential therapeutics. Full article
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