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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 -
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 -
Journal de Mycologie Medicale Mar 2022To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru.
OBJECTIVES
To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru.
METHODS
A cross sectional study was performed. Infants less than seven months old, without any underlying medical conditions attending the "well baby" outpatient clinic at one hospital in Lima, Peru were prospectively enrolled during a 15-month period from November 2016 to February 2018. All had a nasopharyngeal aspirate (NPA) for detection of P. jirovecii DNA using a PCR assay, regardless of respiratory symptoms. P. jirovecii DNA detection was considered to represent pulmonary colonization contemporaneous with Pneumocystis primary infection. Associations between infants' clinical and demographic characteristics and results of P. jirovecii DNA detection were analyzed.
RESULTS
P. jirovecii DNA was detected in 45 of 146 infants (30.8%) and detection was not associated with concurrent respiratory symptoms in 40 of 45 infants. Infants with P. jirovecii had a lower mean age when compared to infants not colonized (p <0.05). The highest frequency of P. jirovecii was observed in 2-3-month-old infants (p < 0.01) and in the cooler winter and spring seasons (p <0.01). Multivariable analysis showed that infants living in a home with ≤ 1 bedroom were more likely to be colonized; Odds Ratio =3.03 (95%CI 1.31-7.00; p = 0.01).
CONCLUSION
Pneumocystis primary infection in this single site in Lima, Peru, was most frequently observed in 2-3-month-old infants, in winter and spring seasons, and with higher detection rates being associated with household conditions favoring close inter-individual contacts and potential transmission of P. jirovecii.
Topics: Cross-Sectional Studies; Humans; Infant; Peru; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 34598108
DOI: 10.1016/j.mycmed.2021.101202 -
La Revue de Medecine Interne May 2016Pneumocystis jiroveci (formerly P. carinii) is an opportunistic fungus responsible for pneumonia in immunocompromised patients. Pneumocystosis in non-HIV-infected... (Review)
Review
Pneumocystis jiroveci (formerly P. carinii) is an opportunistic fungus responsible for pneumonia in immunocompromised patients. Pneumocystosis in non-HIV-infected patients differs from AIDS-associated pneumocystosis in mostly two aspects: diagnosis is more difficult, and prognosis is worse. Hence, efforts should be made to target immunocompromised patients at higher risk of pneumocystosis, so that they are prescribed long-term, low-dose, trimethoprime-sulfamethoxazole, highly effective for pneumocystosis prophylaxis. Patients at highest risk include those with medium and small vessels vasculitis, lymphoproliferative B disorders (chronic or acute lymphocytic leukaemia, non-Hodgkin lymphoma), and solid cancer on long-term corticosteroids. Conversely, widespread use of prophylaxis in all patients carrier of inflammatory diseases on long-term corticosteroids is not warranted. The management of pneumocystosis in non-AIDS immunocompromised patients follows the rules established for AIDS patients. The diagnosis relies on the detection of P. jiroveci cyst on respiratory samples, while PCR does not reliably discriminate infection from colonization, in 2015. High-doses trimethoprim-sulfamethoxazole is, by far, the treatment of choice. The benefit of adjuvant corticosteroid therapy for hypoxic patients, well documented in AIDS patients, has a much lower level of evidence in non-HIV-infected patients, most of them being already on corticosteroid by the time of pneumocystosis diagnosis anyway. However, based on its striking impact on morbi-mortality in AIDS patients, adjuvant corticosteroid is recommended in hypoxic, non-HIV-infected patients with pneumocystosis by many experts and scientific societies.
Topics: Adrenal Cortex Hormones; Antibiotic Prophylaxis; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 26644039
DOI: 10.1016/j.revmed.2015.10.002 -
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 -
Frontiers in Immunology 2023With the extensive use of immunosuppressants, immunosuppression-associated pneumonitis including (PCP) has received increasing attention. Though aberrant adaptive...
INTRODUCTION
With the extensive use of immunosuppressants, immunosuppression-associated pneumonitis including (PCP) has received increasing attention. Though aberrant adaptive immunity has been considered as a key reason for opportunistic infections, the characteristics of innate immunity in these immunocompromised hosts remain unclear.
METHODS
In this study, wild type C57BL/6 mice or dexamethasone-treated mice were injected with or without . Bronchoalveolar lavage fluids (BALFs) were harvested for the multiplex cytokine and metabolomics analysis. The single-cell RNA sequencing (scRNA-seq) of indicated lung tissues or BALFs was performed to decipher the macrophages heterogeneity. Mice lung tissues were further analyzed via quantitative polymerase chain reaction (qPCR) or immunohistochemical staining.
RESULTS
We found that the secretion of both pro-inflammatory cytokines and metabolites in the -infected mice are impaired by glucocorticoids. By scRNA-seq, we identified seven subpopulations of macrophages in mice lung tissues. Among them, a group of Mmp12 macrophages is enriched in the immunocompetent mice with infection. Pseudotime trajectory showed that these Mmp12 macrophages are differentiated from Ly6c classical monocytes, and highly express pro-inflammatory cytokines elevated in BALFs of -infected mice. , we confirmed that dexamethasone impairs the expression of , , and , as well as the fungal killing capacity of alveolar macrophage (AM)-like cells. Moreover, in patients with PCP, we found a group of macrophages resembled the aforementioned Mmp12 macrophages, and these macrophages are inhibited in the patient receiving glucocorticoid treatment. Additionally, dexamethasone simultaneously impaired the functional integrity of resident AMs and downregulated the level of lysophosphatidylcholine, leading to the suppressed antifungal capacities.
CONCLUSION
We reported a group of Mmp12 macrophages conferring protection during infection, which can be dampened by glucocorticoids. This study provides multiple resources for understanding the heterogeneity and metabolic changes of innate immunity in immunocompromised hosts, and also suggests that the loss of Mmp12 macrophages population contributes to the pathogenesis of immunosuppression-associated pneumonitis.
Topics: Mice; Animals; Macrophages, Alveolar; Pneumonia, Pneumocystis; Transcriptome; Glucocorticoids; Matrix Metalloproteinase 12; Multiomics; Mice, Inbred C57BL; Pneumocystis; Cytokines; Immunocompromised Host; Dexamethasone
PubMed: 37359523
DOI: 10.3389/fimmu.2023.1179094 -
Frontiers in Cellular and Infection... 2020pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those... (Review)
Review
pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those who have undergone an organ transplantation. Moreover, mild infections related to low pulmonary fungal burden, frequently designated as pulmonary colonization, occurs in patients with chronic pulmonary diseases, e.g., cystic fibrosis (CF). Indeed, this autosomal recessive disorder alters mucociliary clearance leading to bacterial and fungal colonization of the airways. This mini-review compiles and discusses available information on and CF. It highlights significant differences in the prevalence of pulmonary colonization in European and Brazilian CF patients. It also describes the microbiota associated with in CF patients colonized by . Furthermore, we have described genomic diversity in colonized CF patients. In addition of pulmonary colonization, it appears that PCP can occur in CF patients specifically after lung transplantation, thus requiring preventive strategies. In other respects, primary infection is a worldwide phenomenon occurring in non-immunosuppressed infants within their first months. The primary infection is mostly asymptomatic but it can also present as a benign self-limiting infection. It probably occurs in the same manner in CF infants. Nonetheless, two cases of severe primary infection mimicking PCP in CF infants have been reported, the genetic disease appearing in these circumstances as a risk factor of PCP while the host-pathogen interaction in older children and adults with pulmonary colonization remains to be clarified.
Topics: Adult; Brazil; Child; Cystic Fibrosis; Humans; Infant; Lung; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 33117730
DOI: 10.3389/fcimb.2020.571253