scholarly journals Current State of Carbohydrate Recognition and C-Type Lectin Receptors in Pneumocystis Innate Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Theodore J. Kottom ◽  
Eva M. Carmona ◽  
Andrew H. Limper
Keyword(s):  
Immune Response ◽  
Fungal Pathogens ◽  
Surface Glycoprotein ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Lectin Receptors ◽  
Major Surface Glycoprotein ◽  
Current State ◽  
Major Surface ◽  
Wall Components

Pneumocystis jirovecii is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism’s cell wall components including β-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/Pneumocystis interactions.

scholarly journals Myeloid C-type lectin receptors that recognize fungal mannans interact with Pneumocystis organisms and major surface glycoprotein

2019 ◽  
Vol 68 (11) ◽  
pp. 1649-1654 ◽  
Author(s):  
Theodore J. Kottom ◽  
Deanne M. Hebrink ◽  
Joao T. Monteiro ◽  
Bernd Lepenies ◽  
Eva M. Carmona ◽  
...  
Keyword(s):  
Surface Glycoprotein ◽  
Lectin Receptors ◽  
Major Surface Glycoprotein ◽  
Major Surface

scholarly journals The Fungal PCR Initiative's evaluation of in-house and commercial Pneumocystis jirovecii qPCR assays: Toward a standard for a diagnostics assay

2019 ◽  
Vol 58 (6) ◽  
pp. 779-788 ◽  
Author(s):  
Maud Gits-Muselli ◽  
P Lewis White ◽  
Carlo Mengoli ◽  
Sharon Chen ◽  
Brendan Crowley ◽  
...  
Keyword(s):  
Target Genes ◽  
Clinical Care ◽  
Large Subunit ◽  
Reference Method ◽  
Pneumocystis Pneumonia ◽  
Surface Glycoprotein ◽  
Pneumocystis Jirovecii ◽  
Tubulin Genes ◽  
Major Surface Glycoprotein ◽  
Major Surface

Abstract Quantitative real-time PCR (qPCR) is increasingly used to detect Pneumocystis jirovecii for the diagnosis of Pneumocystis pneumonia (PCP), but there are differences in the nucleic acids targeted, DNA only versus whole nucleic acid (WNA), and also the target genes for amplification. Through the Fungal PCR Initiative, a working group of the International Society for Human and Animal Mycology, a multicenter and monocenter evaluation of PCP qPCR assays was performed. For the multicenter study, 16 reference laboratories from eight different countries, performing 20 assays analyzed a panel consisting of two negative and three PCP positive samples. Aliquots were prepared by pooling residual material from 20 negative or positive- P. jirovecii bronchoalveolar lavage fluids (BALFs). The positive pool was diluted to obtain three concentrations (pure 1:1; 1:100; and 1:1000 to mimic high, medium, and low fungal loads, respectively). The monocenter study compared five in-house and five commercial qPCR assays testing 19 individual BALFs on the same amplification platform. Across both evaluations and for all fungal loads, targeting WNA and the mitochondrial small sub-unit (mtSSU) provided the earliest Cq values, compared to only targeting DNA and the mitochondrial large subunit, the major surface glycoprotein or the beta-tubulin genes. Thus, reverse transcriptase-qPCR targeting the mtSSU gene could serve as a basis for standardizing the P. jirovecii load, which is essential if qPCR is to be incorporated into clinical care pathways as the reference method, accepting that additional parameters such as amplification platforms still need evaluation.

scholarly journals Pneumocystis carinii Major Surface Glycoprotein Dampens Macrophage Inflammatory Responses to Fungal β-Glucan

2020 ◽  
Vol 222 (7) ◽  
pp. 1213-1221
Author(s):  
Theodore J Kottom ◽  
Deanne M Hebrink ◽  
Eva M Carmona ◽  
Andrew H Limper
Keyword(s):  
Protein Complex ◽  
Inflammatory Responses ◽  
Pneumocystis Carinii ◽  
Surface Protein ◽  
Surface Glycoprotein ◽  
Immune Recognition ◽  
Lectin Receptors ◽  
Major Surface Glycoprotein ◽  
Tnf Α ◽  
Major Surface

Abstract Background Pneumocystis major surface glycoprotein (Msg) is a 120-kD surface protein complex on the organism with importance in adhesion and immune recognition. In this study, we show that Msg significantly impairs tumor necrosis factor (TNF)-α secretion by macrophages induced by Saccharomyces cerevisiae and Pneumocystis carinii (Pc) β-glucans. Methods Major surface glycoprotein was shown to greatly reduce β-glucan-induced Dectin-1 immunoreceptor tyrosine-based activating motif (ITAM) phosphorylation. Major surface glycoprotein also down regulated Dectin-1 receptor messenger ribonucleic acid (mRNA) expression in the macrophages. It is interesting that Msg incubation with macrophages resulted in significant mRNA upregulation of both C-type lectin receptors (CLR) Mincle and MCL in Msg protein presence alone but to even greater amounts in the presence of Pc β-glucan. Results The silencing of MCL and Mincle resulted in TNF-α secretions similar to that of macrophages treated with Pneumocystis β-glucan alone, which is suggestive of an inhibitory role for these 2 CLRs in Msg-suppressive effects on host cell immune response. Conclusions Taken together, these data indicate that the Pneumocystis Msg surface protein complex can act to suppress host macrophage inflammatory responses to the proinflammatory β -glucan components of the organisms.

scholarly journals Use of Oropharyngeal Washes to Diagnose and Genotype Pneumocystis jirovecii

2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Jonathan J. Juliano ◽  
Eric Barnett ◽  
Christian M. Parobek ◽  
Steve M. Taylor ◽  
Steven R. Meshnick ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
High Sensitivity ◽  
Diagnostic Techniques ◽  
Surface Glycoprotein ◽  
Pneumocystis Jirovecii ◽  
Major Surface Glycoprotein ◽  
Immunodeficiency Virus ◽  
Noninvasive Samples ◽  
Strain Type ◽  
Major Surface

Abstract Pneumocystis jirovecii is a symbiotic respiratory fungus that presents in 2 clinical forms: pneumonia in immunocompromised patients or colonization, defined by the presence of the organism without associated clinical symptoms. Currently, diagnosis requires invasive bronchoscopy, which may not be available in some settings and is inappropriate for detecting colonization in healthy individuals. Noninvasive diagnostic techniques and molecular strain typing tools that can be used on these samples are critical for conducting studies to better understand transmission. We evaluated 2 real-time polymerase chain reaction (PCR) assays targeting dihydropteroate synthase and the major surface glycoprotein for detection in 77 oropharyngeal washes (OPWs) from 43 symptomatic human immunodeficiency virus-infected patients who underwent bronchoscopy. We also evaluated the ability of a new microsatellite (MS) genotyping panel to strain type infections from these samples. Each PCR used individually provided a high sensitivity (>80%) for detection of pneumonia but a modest specificity (<70%). When used in combination, specificity was increased to 100% with a drop in sensitivity (74%). Concentration of organisms by PCR in the OPW tended to be lower in colonized individuals compared with those with pneumonia, but differences in concentration could not clearly define colonization in symptomatic individuals. Oropharyngeal wash samples were genotyped using 6 MSs with ≥4 alleles successfully genotyped in the majority of colonized patients and ≥5 alleles in patients with pneumonia. The MS profile was consistent over time within patients with serial OPWs analyzed. Microsatellite genotyping on noninvasive samples may aid in studying the molecular epidemiology of this pathogen without requiring invasive diagnostic techniques.

scholarly journals Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e51545 ◽  
Author(s):  
Robert J. Blount ◽  
Leah G. Jarlsberg ◽  
Kieran R. Daly ◽  
William Worodria ◽  
J. Lucian Davis ◽  
...  
Keyword(s):  
Respiratory Symptoms ◽  
Surface Glycoprotein ◽  
Pneumocystis Jirovecii ◽  
Major Surface Glycoprotein ◽  
Major Surface
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