Immune Response to Influenza Infection
Lead Research Organisation:
MRC National Inst for Medical Research
Abstract
We study immune responses to Influenza infection and how the immune system contributes to damage and protection of the patient. Influenza, commonly called the Flu, and other infections of throat and lung are often harmless but sometimes lead to severe damage and even death. Different Flu viruses cause disease of different severity, indicating that viral factors influence disease outcome. Also, when different persons are infected by the same Flu virus, the clinical outcome can vary widely, showing that factors in the individuals body make a difference in the disease. The immune system is necessary to eliminate the virus but in the process contributes to lung damage. The rules in this battle between virus and immune system are not clear, and therefore, the outcome of infection cannot be predicted. Which factors can tip the balance between damage or death on one side and successful clearance of the virus on the other is not completely known. Our studies serve to understand better which characteristics of the virus and of the infected organism can change disease outcome. We attempt to identify factors that contribute to eliciting a strong immune response and to causing lung damage. Better knowledge of these factors will help design better medical intervention during Flu infection.
Technical Summary
We study early immune events in Influenza infection, specifically the interface between infected lung epithelium and innate immunity. The aim of our studies is to identify determinants of immunogenicity and pathogenicity in influenza virus infection and the immune response to it. Respiratory tract infections by bacteria and viruses are still one of the leading causes of death worldwide. Among these infections, seasonal influenza epidemics represent a constant burden to public health, and influenza pandemics caused by new strains pose a serious global threat. Despite this, it is largely unclear which mechanisms can tip the balance between self-limiting infection on one hand and morbidity and mortality due to lung pathology on the other hand. Influenza virus itself is cytopathic, and the immune response is necessary to eliminate the virus, but also involved in immune-mediated damage to lung tissue. It is still unclear how infected epithelial cells activate the immune system, how early events in the infection influence the induction of the immune response, and which viral and host factors are determinants for a protective or fatal outcome of infection. Work in this programme focuses on these early events and on the relationship between infected epithelial cells and immune cells. We have set up airway epithelial cell cultures from primary cells and now study how they activate innate immunity. In vitro work will be done both with wild-type and mutant murine cells and with human cells. These studies will be complemented by in vivo work using bone-marrow chimeras to assess the contribution of epithelial cells to the onset of anti-influenza immune responses. We will attempt to visualize viral infection by reporter gene strategies, to follow infection in vivo and perform functional tests on infected cells. We will assess the role of NK cells and neutrophils in the immune response to and immunopathology caused by influenza virus infection. Since co-infection by gram-positive bacteria is an important clinical complication of influenza infection, we will determine factors by which the viral infection sets the stage for subsequent bacterial attack. All these studies are instrumental to understand respiratory viral infections better, to predict their outcome and to identify modes of intervention that enhance protection and prevent damage.
Organisations
- MRC National Inst for Medical Research, United Kingdom (Lead Research Organisation)
- Albert Ludwig University of Freiburg (Collaboration)
- Aarhus University, Denmark (Collaboration)
- University of Pennsylvania, United States (Collaboration)
- Babraham Institute (Collaboration)
- Rockefeller University (Collaboration)
People |
ORCID iD |
Andreas Wack (Principal Investigator) |
Publications

Aegerter H
(2020)
Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection.
in Nature immunology

Aitken J
(2020)
Scalable and robust SARS-CoV-2 testing in an academic center.
in Nature biotechnology

Bradley KC
(2019)
Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection.
in Cell reports


Cantisani R
(2013)
Toll-like receptor 9-independent responsiveness of human monocytes to microbial DNA.
in Scandinavian journal of immunology

Crotta S
(2014)
The transcription factor E4BP4 is not required for extramedullary pathways of NK cell development.
in Journal of immunology (Baltimore, Md. : 1950)


Davidson S
(2015)
Disease-promoting effects of type I interferons in viral, bacterial, and coinfections.
in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

Davidson S
(2014)
Pathogenic potential of interferon aß in acute influenza infection.
in Nature communications

Davidson S
(2016)
IFN? is a potent anti-influenza therapeutic without the inflammatory side effects of IFNa treatment.
in EMBO molecular medicine
Description | Appointed as scientific expert of the National Belgian Research Fund |
Geographic Reach | National |
Policy Influence Type | Participation in a advisory committee |
Impact | Ensuring high quality of scientific progress in Belgium |
Description | Member of Evaluation Committee for Institut Pasteur Lille, France |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Participation in a advisory committee |
Impact | Evaluation of research and training oat the Institute Pasteur in Lille, France |
Description | CASE studentship |
Amount | £132,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2013 |
End | 06/2018 |
Description | CASE studentship |
Amount | £132,000 (GBP) |
Funding ID | BB/K501475/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2012 |
End | 09/2016 |
Description | Collaboration with GSK |
Amount | £30,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 06/2013 |
End | 12/2013 |
Description | GSK Link Lab post doc position: expression and function of genes associated with Chronic Obstructive Pulmonary Disease |
Amount | £90,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Department | Crick-GSK LinkLabs |
Sector | Private |
Country | United Kingdom |
Start | 01/2018 |
End | 10/2019 |
Description | GSK Link Lab post doc position: function of genes associated with Chronic Obstructive Pulmonary Disease (£ 90000; 2018 - 2019) |
Amount | £180,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 03/2020 |
End | 03/2023 |
Title | Murine model of influenza and bacterial co-infection |
Description | Disease model for the major type of lethality-associated infection in pandemic and seasonal influenza waves |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Provided To Others? | No |
Impact | Allows the study of mechanism behind this common sequela of influenza infection associated with high morbidity and mortality |
Title | Primary murine airway epithelial cell culture |
Description | Lines generated from mouse trachea, can be generated from gene deficient mice |
Type Of Material | Cell line |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | role in influenza infection of single genes can be tested in the primary target cell of the virus |
Description | IFNAR1SA mice |
Organisation | University of Pennsylvania |
Department | School of Veterinary Medicine (UPenn) |
Country | United States |
Sector | Academic/University |
PI Contribution | Analysed in-depth the genetically modified mouse provided to understand impact of prolonged interferon signalling on influenza severity. |
Collaborator Contribution | Provided genetically modified mouse for our studies. |
Impact | common publication in preparation |
Start Year | 2014 |
Description | Interferon lambda |
Organisation | Aarhus University |
Country | Denmark |
Sector | Academic/University |
PI Contribution | Used interferons provided for in vivo studies in infection models and in vitro on human cells. |
Collaborator Contribution | Provided bioactive purified human and mouse interferon lambda. |
Impact | Publication: http://embomolmed.embopress.org/content/8/9/1099.long |
Start Year | 2014 |
Description | Mx mice |
Organisation | Albert Ludwig University of Freiburg |
Country | Germany |
Sector | Academic/University |
PI Contribution | Used tissues and animals provided by the partner in several studies linked to influenza severity and therapy |
Collaborator Contribution | Provided tissues and animals from genetically modified mouse strains |
Impact | Publications: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003773 http://embomolmed.embopress.org/content/8/9/1099.long |
Start Year | 2013 |
Description | Serpin E1 |
Organisation | Rockefeller University |
Country | United States |
Sector | Academic/University |
PI Contribution | Analysed effect of Serpin e1 deficiency in influenza virus control in primary airway epithelia grown from gene-deleted mice. |
Collaborator Contribution | provided tissues for this analysis |
Impact | Publication: http://www.sciencedirect.com/science/article/pii/S009286741500118X |
Start Year | 2014 |
Description | Streptococcus pneumoniae strains |
Organisation | Babraham Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Use S.p. strains to understand long-term changes in lung immunity. |
Collaborator Contribution | Provided range of S.p. strains. |
Impact | Publication in preparation |
Start Year | 2016 |
Title | Interferon lambda as anti-influenza treatment option |
Description | Based on our preclinical studies, we propose that interferon lambda may be a treatment option for severe influenza, as it has potent antiviral effect and does not show the pro-inflammatory side effects that type I interferons show. In vitro tests on human cells confirm the response patterns we have found in vivo in infection models. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Initial development |
Year Development Stage Completed | 2016 |
Development Status | Actively seeking support |
Impact | Based on our preclinical studies, we propose that interferon lambda may be a treatment option for severe influenza, as it has potent antiviral effect and does not show the pro-inflammatory side effects that type I interferons show. In vitro tests on human cells confirm the response patterns we have found in vivo in infection models. |
URL | http://embomolmed.embopress.org/content/8/9/1099.long |
Description | Co-chair of organising committee for Crick meeting: "Influenza 2018: Centenary of the 1918 Pandemic" |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | The most high-profile international scientific conference on Influenza in 2018 focussing around the 1918 Influenza pandemic. |
Year(s) Of Engagement Activity | 2018 |
URL | https://isirv.org/site/index.php/component/content/article/9-events/387-2018-centenary-crick |
Description | Faculty of the Lisbon Spring School in Infection and Immunity |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Faculty at the Spring School in Infection and Immunity 2018: 19-23 March 2018 |
Year(s) Of Engagement Activity | 2018 |
URL | http://twinntoinfect.eu |
Description | Interview to German national newspaper Die Welt |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | German newspaper Die Welt interviewed me and other colleagues to understand better the new ways of collaboration at the Crick institute |
Year(s) Of Engagement Activity | 2017 |
Description | Interviews to several science online newsletters regarding COVID-19 |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Since the role of interferons (IFNs) as treatment for COVID-19 was extensively tested and debated, I was asked for an expert opinion on several publications or clinical trials regarding this. I was also interviewed about our own studies delineating benefits and risks of IFN usage in COVID-19. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Member of the Organisation Committee of "THE LONDON INFECTIONS & IMMUNITY SYMPOSIUM 2018" |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | National scientific conference on progress in infection and immunity research. |
Year(s) Of Engagement Activity | 2018 |
Description | Newspaper coverage of findings on the link between antibiotics and influenza susceptibility |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Wide newspaper coverage of our results showing that antibiotics use can increase influenza susceptibility. Interview with chinese state television. |
Year(s) Of Engagement Activity | 2019 |
Description | Radio interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | German national radio station ARD came to find out about the vision of the Crick, how it is to work here as a German researcher and implications of Brexit. |
Year(s) Of Engagement Activity | 2017 |
Description | Radio interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Interview by BBC 5 radio on our work identifying a molecular link between air pollution and respiratory disease |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.bbc.co.uk/programmes/b07rkgb2 |
Description | School class visiting the institute |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 25 pupils were introduced to the research taking place at the NIMR, to raise interest in a career in academic research and the topics covered here. Following the positive feed back by the class it was agreed to turn this into a regular annual event for subsequent years. |
Year(s) Of Engagement Activity | 2011,2012,2013,2014 |
Description | School visit to institute |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Overview on influenza virus, epidemics and pandemics, and the research concerning influenza we perform here. school reported high interest and satisfaction of the pupils who attended |
Year(s) Of Engagement Activity | 2013 |
Description | Seminar to health professionals about influenza host susceptibility and novel treatment options |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Seminar and discussion at the London-wide Virology discussion group organised by professionals in the clinical sector with the aim of keeping up with recent academic progress. Lively discussion and much interest in the subject and the seminar content. |
Year(s) Of Engagement Activity | 2017 |
Description | Several briefings requested by mainstream media journalists (e.g. BBC) regarding COVID-19 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | On several occasions, BBC journalists were given scientific background to COVID-related questions. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Speaker at the world immunology day focussed on vaccines |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Part of a discussion panel to highlight the success if vaccination in history and the importance of vaccine use in the future. Held in the framework of the Word Immunology Day, organised by Nature Publishing Group and the Crick. |
Year(s) Of Engagement Activity | 2020 |
Description | Television interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | German national television ARD interviewed about the new Crick institute, working conditions there and Brexit implications. |
Year(s) Of Engagement Activity | 2017 |