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Frontiers in Immunology 2023β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics.... (Review)
Review
β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics. β-glucan binds to various cell surface receptors, which produces an inflammatory response and accounts for its immune effects. A deeper comprehension of the processes by β-glucan recognizes its receptors, activates related signaling pathways, and regulates immunity as required. Such understanding will provide a basis for developing new therapies against . Herein, we briefly review the structural composition of β-glucans as a vital component of the cell wall, the host immunity mediated by β-glucans after their recognition, and discuss opportunities for the development of new strategies to combat .
Topics: Pneumocystis; beta-Glucans; Glucans; Pneumonia, Pneumocystis; Cell Wall
PubMed: 36845149
DOI: 10.3389/fimmu.2023.1094464 -
Nanomaterials (Basel, Switzerland) Jun 2020is a fungus responsible for human Pneumocystis pneumonia, one of the most severe infections encountered in immunodepressed individuals. The diagnosis of Pneumocystis...
is a fungus responsible for human Pneumocystis pneumonia, one of the most severe infections encountered in immunodepressed individuals. The diagnosis of Pneumocystis pneumonia continues to be challenging due to the absence of specific symptoms in infected patients. Moreover, the standard diagnostic method employed for its diagnosis involves mainly PCR-based techniques, which besides being highly specific and sensitive, require specialized personnel and equipment and are time-consuming. Our aim is to demonstrate an optical biosensor methodology based on surface plasmon resonance to perform such diagnostics in an efficient and decentralized scheme. The biosensor methodology employs poly-purine reverse-Hoogsteen hairpin probes for the detection of the mitochondrial large subunit ribosomal RNA (mtLSU rRNA) gene, related to detection. The biosensor device performs a real-time and label-free identification of the mtLSU rRNA gene with excellent selectivity and reproducibility, achieving limits of detection of around 2.11 nM. A preliminary evaluation of clinical samples showed rapid, label-free and specific identification of in human lung fluids such as bronchoalveolar lavages or nasopharyngeal aspirates. These results offer a door for the future deployment of a sensitive diagnostic tool for fast, direct and selective detection of Pneumocystis pneumonia disease.
PubMed: 32604931
DOI: 10.3390/nano10061246 -
Current Rheumatology Reports Feb 2020The management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The... (Review)
Review
PURPOSE OF REVIEW
The management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The continued use of corticosteroids, in addition to the rise of combination immunosuppressive therapy, has contributed to the ongoing concern for infection. Perhaps the most feared infection in IIM patients is Pneumocystis jirovecii pneumonia (PJP) given its infrequent occurrence yet high mortality. The field has been, and continues to be, without evidence-based guidelines to help clinicians determine which patients with IIM to prescribe prophylaxis. Herein, we review this literature to provide the clinician with an up-to-date view of infections in IIM.
RECENT FINDINGS
In the past 5 years, a number of studies have been reported highlighting various infectious complications, which help us better understand their frequency and associated risk factors. In addition, data has been published on the potential harms of PJP prophylaxis, to better inform the risk/benefit of our decision-making. Infection remains a major contributor to morbidity and mortality in IIM. A better understanding of which patient subgroups are at risk for particular infections will inform optimal management strategies.
Topics: Antibiotic Prophylaxis; Glucocorticoids; Humans; Immunosuppressive Agents; Incidence; Infection Control; Infections; Myositis; Pneumocystis carinii; Pneumonia, Pneumocystis; Vaccines
PubMed: 32020305
DOI: 10.1007/s11926-020-0883-0 -
American Journal of Respiratory Cell... Jun 2020
Topics: Humans; Macrophage Activation; Pneumocystis; Pneumonia, Pneumocystis; Programmed Cell Death 1 Receptor; Th1 Cells
PubMed: 32109143
DOI: 10.1165/rcmb.2020-0051ED -
Zhongguo Fei Ai Za Zhi = Chinese... Apr 2022In recent years, with the widespread use of immunodepressant agents, Pneumocystis jirovecii pneumonia (PJP) has been significantly found in non-human immunodeficiency... (Review)
Review
In recent years, with the widespread use of immunodepressant agents, Pneumocystis jirovecii pneumonia (PJP) has been significantly found in non-human immunodeficiency virus (HIV) patients, such as those with malignancies, post-transplantation and autoimmune diseases. Although the risk factors and management of PJP have been extensively studied in the hematologic tumor and post-transplant populations, the research on real tumor cases is insufficient. Lung cancer has been the most common tumor with the highest number of incidence and death worldwide, and the prognosis of lung cancer patients infected with PJP is poor in clinical practice. By reviewing the previous studies, this paper summarized the epidemiology and clinical manifestations of PJP in lung cancer patients, the risk factors and possible mechanisms of PJP infection in lung cancer patients, diagnosis and prevention, and other research progresses to provide reference for clinical application. .
Topics: Humans; Incidence; Lung Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors
PubMed: 35340199
DOI: 10.3779/j.issn.1009-3419.2022.101.14 -
JCI Insight Sep 2022Pneumocystis is the most common fungal pulmonary infection in children under the age of 5 years. In children with primary immunodeficiency, Pneumocystis often presents...
Pneumocystis is the most common fungal pulmonary infection in children under the age of 5 years. In children with primary immunodeficiency, Pneumocystis often presents at 3-6 months of age, a time period that coincides with the nadir of maternal IgG and when IgM is the dominant Ig isotype. Because B cells are the dominant antigen-presenting cells for Pneumocystis, we hypothesized the presence of fungal-specific IgMs in humans and mice and that these IgM specificities would predict T cell antigens. We detected fungal-specific IgMs in human and mouse sera and utilized immunoprecipitation to determine whether any antigens were similar across donors. We then assessed T cell responses to these antigens and found anti-Pneumocystis IgM in WT mice, Aicda-/- mice, and in human cord blood. Immunoprecipitation of Pneumocystis murina with human cord blood identified shared antigens among these donors. Using class II MHC binding prediction, we designed peptides with these antigens and identified robust peptide-specific lung T cell responses after P. murina infection. After mice were immunized with 2 of the antigens, adoptive transfer of vaccine-elicited CD4+ T cells showed effector activity, suggesting that these antigens contain protective Pneumocystis epitopes. These data support the notion that germline-encoded IgM B cell receptors are critical in antigen presentation and T cell priming in early Pneumocystis infection.
Topics: Animals; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Germ Cells; Humans; Immunoglobulin M; Lung; Mice; Pneumonia, Pneumocystis
PubMed: 35917185
DOI: 10.1172/jci.insight.161450 -
Clinical and Experimental Medicine Aug 2022Treatment of the novel Coronavirus Disease 2019 (COVID-19) remains a complicated challenge, especially among patients with severe disease. In recent studies,... (Review)
Review
Treatment of the novel Coronavirus Disease 2019 (COVID-19) remains a complicated challenge, especially among patients with severe disease. In recent studies, immunosuppressive therapy has shown promising results for control of the cytokine storm syndrome (CSS) in severe cases of COVID-19. However, it is well documented that immunosuppressive agents (e.g., corticosteroids and cytokine blockers) increase the risk of opportunistic infections. On the other hand, several opportunistic infections were reported in COVID-19 patients, including Aspergillus spp., Candida spp., Cryptococcus neoformans, Pneumocystis jiroveci (carinii), mucormycosis, Cytomegalovirus (CMV), Herpes simplex virus (HSV), Strongyloides stercoralis, Mycobacterium tuberculosis, and Toxoplasma gondii. This review is a snapshot about the main opportunistic infections that reported among COVID-19 patients. As such, we summarized information about the main immunosuppressive agents that were used in recent clinical trials for COVID-19 patients and the risk of opportunistic infections following these treatments. We also discussed about the main challenges regarding diagnosis and treatment of COVID-19-associated opportunistic infections (CAOIs).
Topics: COVID-19; Candidiasis; Cytomegalovirus Infections; Humans; Immunosuppressive Agents; Opportunistic Infections; Pneumonia, Pneumocystis; COVID-19 Drug Treatment
PubMed: 34424451
DOI: 10.1007/s10238-021-00751-7 -
MSphere Sep 2019pneumonia is the most common serious opportunistic infection in patients with HIV/AIDS. Furthermore, pneumonia is a feared complication of the immunosuppressive drug...
pneumonia is the most common serious opportunistic infection in patients with HIV/AIDS. Furthermore, pneumonia is a feared complication of the immunosuppressive drug regimens used to treat autoimmunity, malignancy, and posttransplantation rejection. With an increasing at-risk population, there is a strong need for novel approaches to discover diagnostic and vaccine targets. There are multiple challenges to finding these targets, however. First, has a largely unannotated genome. To address this, we evaluated each protein encoded within the genome by comparisons to proteins encoded within the genomes of other fungi using NCBI BLAST. Second, relies on a multiphasic life cycle, as both the transmissible form (the ascus) and the replicative form (the trophozoite [troph]) reside within the alveolar space of the host. To that end, we purified asci and trophs from and utilized transcriptomics to identify differentially regulated genes. Two such genes, and , are differentially regulated in the ascus and the troph, respectively, and can be utilized to characterize the state of the life cycle , encoding a β-1,3-glucan synthase with a large extracellular domain previously identified using surface proteomics, was more highly expressed on the ascus form of GSC-1 ectodomain immunization generated a strong antibody response that demonstrated the ability to recognize the surface of the asci. GSC-1 ectodomain immunization was also capable of reducing ascus burden following primary challenge with Finally, mice immunized with the GSC-1 ectodomain had limited fungal burden following natural transmission of using a cohousing model. The current report enhances our understanding of biology in a number of ways. First, the current study provided a preliminary annotation of the genome, addressing a long-standing issue in the field. Second, this study validated two novel transcripts enriched in the two predominant life forms of These findings allow better characterization of the life cycle and could be valuable diagnostic tools. Furthermore, this study outlined a novel pipeline of -omics techniques capable of revealing novel antigens (e.g., GSC-1) for the development of vaccines against .
Topics: Animals; Antigens, Fungal; Female; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Genome, Fungal; Lung; Mice; Mice, Inbred C57BL; Pneumocystis; Pneumonia, Pneumocystis; Proteomics; Transcriptome
PubMed: 31484742
DOI: 10.1128/mSphere.00488-19 -
BMJ Open Respiratory Research Mar 2021Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the...
BACKGROUND
Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by has previously been associated with multiple chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and severe asthma (SA). Decreased incidence of pneumonia in HIV-infected individuals and reduced severity of COPD is associated with naturally occurring antibody responses to the antigen, Kexin (KEX1).
METHODS
104 paediatric patients were screened for KEX1 IgG reciprocal end point titre (RET), including 51 with SA, 20 with mild/moderate asthma, 20 non-asthma and 13 with cystic fibrosis (CF) in a cross-sectional study.
RESULTS
Patients with SA had significantly reduced KEX1 titres compared with patients with mild/moderate asthma (p=0.018) and CF (p=0.003). A binary KEX1 RET indicator was determined at a threshold of KEX1 RET=1000. Patients with SA had 4.40 (95% CI 1.28 to 13.25, p=0.014) and 17.92 (95% CI 4.15 to 66.62, p<0.001) times the odds of falling below that threshold compared with mild/moderate asthma and patients with CF, respectively. Moreover, KEX1 IgG RET did not correlate with tetanus toxoid IgG (r=0.21, p=0.82) or total IgE (r=0.03, p=0.76), indicating findings are specific to antibody responses to KEX1.
CONCLUSIONS
Paediatric patients with SA may be at higher risk for chronic infections and asthma symptom exacerbation due to reduced levels of protective antibodies. Plasma KEX1 IgG titre may be a useful parameter in determining the clinical course of treatment for paediatric patients with asthma.
Topics: Antibody Formation; Asthma; Child; Cross-Sectional Studies; Humans; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 33762359
DOI: 10.1136/bmjresp-2020-000842 -
Cureus Aug 2022pneumonia (PCP) is one of the most common opportunistic infections worldwide that affects the lung. leads to pneumonia, caused by , formerly known as . In recent... (Review)
Review
pneumonia (PCP) is one of the most common opportunistic infections worldwide that affects the lung. leads to pneumonia, caused by , formerly known as . In recent decades, PCP has been a major health problem for human immunodeficiency virus (HIV) patients and is responsible for most of mortality and morbidity. However, the increasing number of immunosuppressive-related diseases has led to outbreaks in other patient populations, raising the concern for PCP as it becomes a major concern among those patients. These changes led to marked changes in the prevalence and mortality rates of PCP. Huge variations in those parameters among HIV and non-HIV patients have been seen also. Historically, the diagnosis was made by staining and direct visualization of the organism within the bronchoalveolar lavage (BAL) fluid. The diagnosis is now made by microscopic examination and a real-time polymerase chain reaction (PCR) of BAL. Serum (1,3)-β-D-glucan, which is a component of the cell wall that distinguishes it from other fungi, has become an important diagnostic tool. Early diagnosis and treatment play a vital role in the patient's survival and in the infection outcome; hence, empirical PCP therapy should be started immediately when the infection is suspected without waiting for the results of the diagnostic test. Steroids play an important role in the treatment of HIV patients, especially patients who present with hypoxia and respiratory failure. Prophylaxis is very effective and should be given to all patients at high risk of PCP. Antiretroviral therapy (ART) should be started as soon as possible in newly diagnosed HIV-infected patients with PCP, and the immune status of immunocompromised patients with PCP should be improved by temporarily withholding immunosuppressive drugs or reducing their doses.
PubMed: 36106266
DOI: 10.7759/cureus.27727