Short-term repeated HRV-16 exposure results in an attenuated immune response in vivo in humans

Rebecca M Koch; Matthijs Kox; Corné van den Kieboom; Gerben Ferwerda; Jelle Gerretsen; Sandra Ten Bruggencate; Johannes G van der Hoeven; Marien I de Jonge; Peter Pickkers

doi:10.1371/journal.pone.0191937

Short-term repeated HRV-16 exposure results in an attenuated immune response in vivo in humans

PLoS One. 2018 Feb 15;13(2):e0191937. doi: 10.1371/journal.pone.0191937. eCollection 2018.

Authors

Rebecca M Koch^{1

2}, Matthijs Kox^{1

2}, Corné van den Kieboom^{2

3}, Gerben Ferwerda^{2

3}, Jelle Gerretsen^{1

2}, Sandra Ten Bruggencate⁴, Johannes G van der Hoeven^{1

2}, Marien I de Jonge^{2

3}, Peter Pickkers^{1

2}

Affiliations

¹ Radboudumc, HB, Radboud Institute for Molecular Life Sciences, Department of Intensive Care Medicine, HB, Nijmegen, The Netherlands.
² Radboud center for Infectious Diseases (RCI), HB, Nijmegen, The Netherlands.
³ Radboudumc, HB, Radboud Institute for Molecular Life Sciences, Department of Pediatrics, HB, Nijmegen, The Netherlands.
⁴ NIZO food research BV, ZB, Ede, The Netherlands.

Abstract

Introduction: Naturally, development of adaptive immunity following HRV infection affects the immune response. However, it is currently unclear whether or not HRV re-exposure within a short time frame leads to an altered innate immune response. The "experimental cold model" is used to investigate the pathogenesis of HRV infection and allows us to investigate the effects of repeated exposure on both local and systemic innate immunity.

Methods: 40 healthy male and female (1:1) subjects were nasally inoculated with HRV-16 or placebo. One week later, all subjects received HRV-16. Baseline seronegative subjects (n = 18) were included for further analysis.

Results: Infection rate was 82%. Primary HRV infection induced a marked increase in viral load and IP-10 levels in nasal wash, while a similar trend was observed for IL-6 and IL-10. Apart from an increase in IP-10 plasma levels, HRV infection did not induce systemic immune effects nor lower respiratory tract inflammation. With similar viral load present during the second HRV challenge, IP-10 and IL-6 in nasal wash showed no increase, but gradually declined, with a similar trend for IL-10.

Conclusion: Upon a second HRV challenge one week after the first, a less pronounced response for several innate immune parameters is observed. This could be the result of immunological tolerance and possibly increases vulnerability towards secondary infections.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Common Cold / immunology*
Common Cold / physiopathology
Common Cold / virology
Cytokines / metabolism
Female
Humans
Male
Nasal Cavity / metabolism
Placebos
Rhinovirus / isolation & purification
Rhinovirus / pathogenicity*
Viral Load

Substances

Cytokines
Placebos

Grants and funding

This work was supported by an EFRO grant (2011-013287). StB is an employee of NIZO food research BV, a commercial party that participated in this EFRO grant. EFRO provided support in the form of salaries for authors [RMK, MK, StB, MIdJ, PP] and research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Apart from the design and analysis of the online symptom diary and review of the manuscript, NIZO food research BV, in the person of StB, did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of all authors are articulated in the 'author contributions' section.