An Emerging Role of B Cell Immunity in Susceptibility to <i>Pneumocystis</i> Pneumonia

Kolls, Jay K.

doi:10.1165/rcmb.2016-0360ed

Cited by 13 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Susceptibility to Pneumocystis is also influenced by B cells, which play a dual role in antibody production and antigen presentation [53]. Firstly, B cells are important in T cell priming during the primary stage of Pneumocystis infection.…”

Section: Lymphocytes: Cd4+ T Cells Cd8+ T Cells and B Cellsmentioning

confidence: 99%

The Contribution of Host Cells to Pneumocystis Immunity: An Update

2019

View full text Add to dashboard Cite

Pneumocystis is a ubiquitous atypical fungus that is distributed globally. The genus comprises morphologically similar but genetically heterogeneous species that have co-evolved with specific mammalian hosts as obligate intra-pulmonary pathogens. In humans, Pneumocystis jirovecii is the causative organism of Pneumocystis pneumonia (PCP) in immunocompromised individuals, a serious illness frequently leading to life-threatening respiratory failure. Initially observed in acquired immunodeficiency syndrome (AIDS) patients, PCP is increasingly observed in immunocompromised non-AIDS patients. The evolving epidemiology and persistently poor outcomes of this common infection will require new strategies for diagnosis and treatment. A deeper understanding of host immune responses and of the cells that mediate them will improve the chance of developing new treatment strategies. This brief review provides an update on recent studies on the role of host immunity against Pneumocystis.

show abstract

Section: Lymphocytes: Cd4+ T Cells Cd8+ T Cells and B Cellsmentioning

confidence: 99%

The Contribution of Host Cells to Pneumocystis Immunity: An Update

2019

View full text Add to dashboard Cite

show abstract

“…B cells have been demonstrated to play a vital role in host defense against Pneumocystis infection by antigen presentation and antibody production (Kolls, 2017;Otieno-Odhiambo et al, 2019). The B cell receptor (BCR), a B cell surface membrane immunoglobulin, possesses the ability to specifically recognize and bind antigens, with the complementarity-determining region 3 (CDR3) of the heavy chain as the major determinant of antibody specificity (Xu and Davis, 2000).…”

Section: Introductionmentioning

confidence: 99%

Signatures of B Cell Receptor Repertoire Following Pneumocystis Infection

et al. 2021

View full text Add to dashboard Cite

B cells play vital roles in host defense against Pneumocystis infection. However, the features of the B cell receptor (BCR) repertoire in disease progression remain unclear. Here, we integrated single-cell RNA sequencing and single-cell BCR sequencing of immune cells from mouse lungs in an uninfected state and 1–4 weeks post-infection in order to illustrate the dynamic nature of B cell responses during Pneumocystis infection. We identified continuously increased plasma cells and an elevated ratio of (IgA + IgG) to (IgD + IgM) after infection. Moreover, Pneumocystis infection was associated with an increasing naïve B subset characterized by elevated expression of the transcription factor ATF3. The proportion of clonal expanded cells progressively increased, while BCR diversity decreased. Plasma cells exhibited higher levels of somatic hypermutation than naïve B cells. Biased usage of V(D)J genes was observed, and the usage frequency of IGHV9-3 rose. Overall, these results present a detailed atlas of B cell transcriptional changes and BCR repertoire features in the context of Pneumocystis infection, which provides valuable information for finding diagnostic biomarkers and developing potential immunotherapeutic targets.

show abstract

“…Intranasal administration of 4F11, an mAb that recognizes the Pneumocystis kexin-like protein KEX1, was able to prevent transmission of Pneumocystis pneumonia from infected to susceptible cohoused mice, demonstrating the feasibility of this approach [110]. Emerging evidence of the importance of B cellmediated immunity to Pneumocystis infection strongly supports further research in this area [111].…”

Section: Fungal Infectionsmentioning

confidence: 89%

Reassessing therapeutic antibodies for neglected and tropical diseases

et al. 2020

View full text Add to dashboard Cite

In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators. The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology. Other recent successes have included new antibodies for use in viral diseases, including HIV. The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty. However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited. Recent technology developments also indicate that several months of protection could be achieved with a single dose. Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients. This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.PLOS Neglected Tropical Diseases | https://doi.interactions have proved difficult to block. In addition, there has been great progress in the development of technology. Early generations of antibodies for human use were developed from mAbs developed in mice, antibodies that were then humanized. Recently, the technology used peptide and antibody display on phages, for which part of the 2018 Nobel Prize in Chemistry was awarded to Sir Gregory P. Winter [6]. More recently, new technologies have been developed to clone antibodies from memory B cells [7] or plasma B cells [8, 9], allowing the isolation of individual antibodies from patients with viral infections-approaches that can be applied to any infectious disease.A second reason for the popularity of antibodies in recent years is their success rate in clinical development. Once an antibody reaches testing in humans, it has a success rate of 17% to 25% for approval as a new medicine [10], compared with 5% to 10% for small molecules. This success rate is partly due to the exquisite selectivity of mAbs, enabling them to distinguish between closely related molecular targets. In the case of infectious disease, this selectivity can be absolute, since antibodies can be generated that are specific for the invading pathogen and do not cross-react with host tissues. This lack of cross-reactivity with human tissue can be confirmed by immunohistochemistry on both adult and embryonic tissues prior to the start of clinical trials. This is in stark contrast to small molecules, in which sometimes unexpected onand off-target safety signals are frequently seen in the later stages of clinical development, resulting in expensive late-stage attrition. In addition, antibodies show a relatively narrow range of variation in pharmacokinetic exposure, facilitating early estimation of the human effective dose. This is unlike true xenobiotics, whose metabolism an...

show abstract

An Emerging Role of B Cell Immunity in Susceptibility to Pneumocystis Pneumonia

Cited by 13 publications

References 19 publications

The Contribution of Host Cells to Pneumocystis Immunity: An Update

The Contribution of Host Cells to Pneumocystis Immunity: An Update

Signatures of B Cell Receptor Repertoire Following Pneumocystis Infection

Reassessing therapeutic antibodies for neglected and tropical diseases

Contact Info

Product

Resources

About