Influenza coinfection inhibits control of mycobacterial infection in a human challenge model

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Mycobacterium tuberculosis infection is a dynamic continuum. Clinical outcomes reflect complex host-pathogen interactions. Epidemiological and animal studies have suggested influenza coinfection as a risk factor for progression from contained infection to active disease, but human studies have been lacking. Using a whole blood luminescent mycobacterial growth inhibition assay within a human influenza challenge study, we show that influenza infection reduces immunological control of mycobacterial growth. Transcriptome-wide RNA sequencing, cytokine and cellular analyses of subjects’ blood before and after influenza infection reveal that innate immune pathways, including type 1 interferon signalling, are activated by influenza but their subsequent responsiveness to mycobacteria is reduced, with multiple genes’ responses to BCG lux infection repressed by influenza coinfection. Our data suggest that influenza infection impairs immune mechanisms that contain mycobacterial growth and may be a risk factor for tuberculosis (TB) disease. Influenza vaccination might offer high risk, high prevalence populations protection against TB disease.
Funding Information
  • Wellcome (206508/Z/17/Z)
  • Medical Research Foundation (MRF-160-0008-ELP-KAFO-C0801)
  • Rosetrees Trust (Major Grant PGL22/100101)
  • National Institute of Allergy and Infectious Diseases ((Centers of Excellence for Influenza Research and Surveillance. Contract no. HHSN272201400008C))
  • Defense Advanced Research Projects Agency (Contract no. 140D6319C00236)
  • European Commission (DIAMONDS (Horizon 2020; grant 848196) and PERFORM (Horizon 2020 grant 668303))
  • National Institute for Health and Care Research (see below)
  • Wellcome 4i NIHR Imperial BRC PhD Fellowship, grant RDA02 NIHR Imperial Biomedical Research Centre NIHR Imperial Clinical Research Facility Kwok Foundation

This publication has 72 references indexed in Scilit: