Pathogen manipulation of B cells: the best defence is a good offence

Nothelfer, Katharina; Sansonetti, Philippe J.; Phalipon, Armelle

doi:10.1038/nrmicro3415

Cited by 79 publications

(71 citation statements)

References 107 publications

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“…B cell interactions with pathogens without antigen specificity usually leads to B cell death and an impaired antibody responses (Nothelfer et al, 2015). RSV infects nBreg cells, through IgM recognition and induced CX3CR1 allowing viral interaction with the G glycoprotein.…”

Section: Discussionmentioning

confidence: 99%

Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity

et al. 2017

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Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production. In the respiratory tract of neonates with severe RSV-induced acute bronchiolitis, RSV-infected nBreg cell frequencies correlated with increased viral load and decreased blood memory Th1 cell frequencies. Thus, the frequency of nBreg cells is predictive of the severity of acute bronchiolitis disease and nBreg cell activity may constitute an early-life host response that favors microbial pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity

et al. 2017

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“…Variability in the host immune response to infection, particularly with regard to genotype (58) and immune regulation during infection (59), remains an important challenge, with implications both for developing diagnostics based on the immune response and for understanding disease risk associated with this variability. Additionally, some pathogens, such as malaria, Epstein–Barr virus, and others, subvert the B cell-mediated response, resulting in chronic infections (120). Alternatively, pathogens such as dengue virus appear to augment the numerical ASC response to infection, resulting in severe immunopathology (95).…”

Section: Future Study and Clinical Applicationsmentioning

confidence: 99%

The Antibody-Secreting Cell Response to Infection: Kinetics and Clinical Applications

Carter

Mitchell

Sauteur³

et al. 2017

Front. Immunol.

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Despite the availability of advances in molecular diagnostic testing for infectious disease, there is still a need for tools that advance clinical care and public health. Current methods focus on pathogen detection with unprecedented precision, but often lack specificity. In contrast, the host immune response is highly specific for the infecting pathogen. Serological studies are rarely helpful in clinical settings, as they require acute and convalescent antibody testing. However, the B cell response is much more rapid and short-lived, making it an optimal target for determining disease aetiology in patients with infections. The performance of tests that aim to detect circulating antigen-specific antibody-secreting cells (ASCs) has previously been unclear. Test performance is reliant on detecting the presence of ASCs in the peripheral blood. As such, the kinetics of the ASC response to infection, the antigen specificity of the ASC response, and the methods of ASC detection are all critical. In this review, we summarize previous studies that have used techniques to enumerate ASCs during infection. We describe the emergence, peak, and waning of these cells in peripheral blood during infection with a number of bacterial and viral pathogens, as well as malaria infection. We find that the timing of antigen-specific ASC appearance and disappearance is highly conserved across pathogens, with a peak response between day 7 and day 8 of illness and largely absent following day 14 since onset of symptoms. Data show a sensitivity of ~90% and specificity >80% for pathogen detection using ASC-based methods. Overall, the summarised work indicates that ASC-based methods may be very sensitive and highly specific for determining the etiology of infection and have some advantages over current methods. Important areas of research remain, including more accurate definition of the timing of the ASC response to infection, the biological mechanisms underlying variability in its magnitude and the evolution and the B cell receptor in response to immune challenge. Nonetheless, there is potential of the ASC response to infection to be exploited as the basis for novel diagnostic tests to inform clinical care and public health priorities.

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“…Then, Roberto Burioni et al report on virus-induced autoimmunity via subversion of antibody gene usage, a new intriguing exploitation of the humoral response which has never before been thoroughly reviewed. It is noteworthy that the manipulation exerted by pathogens on other critical actors or cellular processes of the immune system have recently been reviewed, for example NK cells [7], B cells [8], complement [9], autophagy [10], cytokine network [11], or costimulatory molecules [12].…”

Section: Editorialmentioning

confidence: 99%