Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies
Mar Naranjo-Gomez, … , Marc Piechaczyk, Mireia Pelegrin
Mar Naranjo-Gomez, … , Marc Piechaczyk, Mireia Pelegrin
Published May 3, 2018
Citation Information: JCI Insight. 2018;3(9):e97339. https://doi.org/10.1172/jci.insight.97339.
View: Text | PDF
Research Article Infectious disease Therapeutics

Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies

  • Text
  • PDF
Abstract

Using a mouse retroviral model, we have shown that mAb-based immunotherapy can induce life-long endogenous protective immunity (vaccine-like effects). This observation has potentially important consequences for treating life-threatening human viral infections. Here, we investigated the role of neutrophils in this effect. Neutrophils are innate immunity effector cells with well-established microbe-killing activities that are rapidly mobilized upon infection. They are also emerging as orchestrators of innate and adaptive immunities. However, their immunomodulatory activity during antiviral mAb immunotherapies has never been studied. Our data reveal that neutrophils have an essential role in immunotherapy-induced immune protection of infected mice. Unexpectedly, neutrophils have a limited effect in controlling viral propagation upon passive immunotherapy administration, which is mostly mediated by NK cells. Instead, neutrophils operate as essential inducers of a potent host humoral antiviral response. Thus, neutrophils play an unexpected key role in protective immunity induction by antiviral mAbs. Our work opens approaches to improve antiviral immunotherapies, as it suggests that preserving neutrophil functions and counts might be required for achieving mAb-induced protective immunity.

Authors

Mar Naranjo-Gomez, Jennifer Lambour, Marc Piechaczyk, Mireia Pelegrin

×

Figure 6

Effects of neutrophil depletion on B cell responses.

Options: View larger image (or click on image) Download as PowerPoint
Effects of neutrophil depletion on B cell responses.
Neutrophils of naiv...
Neutrophils of naive, I/NT, and I/T mice were depleted, or not, as indicated in Figure 1A. (A and B) Frequency of MZ and follicular (FO) B cells. Spleen cells were isolated at day 14 p.i. and were analyzed by flow cytometry for the frequency of MZ (CD21hiIgMhi) (A) and FO (CD23+IgMlo) (B) CD19+ B cells, as depicted in the gating strategy. (C) Frequency of plasma cells. BM cells were isolated at day 14 p.i. and were analyzed by flow cytometry for the frequency of CD138+ (CD19+) B cells. The data represent 5 independent experiments, with 7–12 mice per group for naive mice and 17–21 per group for I/NT and I/T mice. Data are expressed as mean ± SEM. Statistical significance was established using a parametric 1-way ANOVA test with a Bonferroni correction (*P < 0.05; **P < 0.01; ***P < 0.001). (D) Histological analyses of spleen sections. Immunolabeling of B cells (B220+) and macrophages of the MZ (CD169+) was performed in sections from spleens of infected/nontreated and infected/treated mice (depleted or not of neutrophils) recovered at 14 days p.i. to visualize germinal centers. The images are representative of 4 separate mice for each experimental condition. Scale bar: 200 μm.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts