IFNγ blockade in Mycobacterium tuberculosis infected macaques alters the granuloma environment but not bacterial control
FDG-PET/CT scores and broadly enhanced anti-viral-like inflammatory responses. Strikingly, IFNγR1 blockade for the first three months of infection had no impact on bacterial loads despite suppression of bioactive IFNγ in granulomas and changes to host immune responses and granuloma structure. We find individuals from Mtb endemic regions with anti-IFNγ neutralizing autoantibodies who develop NTM disease and not TB despite evidence of previous exposure to Mtb. Lastly, we show that mice over-estimate the importance IFNγ in host resistance to TB due to a species-specific induction of iNOS by IFNγ. Thus, while IFNγ has immunoregulatory effects in granulomas, normal resistance to TB in macaques and humans likely requires little IFNγR1 signaling during infection, indicating that the major mechanisms of adaptive immunity to Mtb infection remain unknown.
Authors
- Laura E. Via (ORCID: https://orcid.org/0000-0001-6074-9521)
- Christine E Nelson (ORCID: https://orcid.org/0000-0003-3879-9105)
- Sivaranjani Namasivayam (ORCID: https://orcid.org/0000-0001-9993-1347)
- A Sher
- Ploenchan Chetchotisakd (ORCID: https://orcid.org/0000-0001-9501-5827)
- Daniel L. Barber (ORCID: https://orcid.org/0000-0001-7008-7509)
- Steven M. Holland (ORCID: https://orcid.org/0000-0003-3207-5464)
- Artur T. L. Queiroz (ORCID: https://orcid.org/0000-0003-4908-9993)
- Carl G. Feng (ORCID: https://orcid.org/0000-0003-4301-4640)
- Keith D. Kauffman (ORCID: https://orcid.org/0000-0001-7208-1565)
- Eduardo R. Fukutani (ORCID: https://orcid.org/0000-0001-6326-8731)
- Katrin D. Mayer-Barber
- Christa S. Zerbe (ORCID: https://orcid.org/0000-0003-4219-0503)
- J. Ernst (ORCID: https://orcid.org/0000-0001-9951-6207)
- Erin F. McCaffrey
- Shunsuke Sakai
- Jay Buchanan
- Bruno B. Andrade (ORCID: https://orcid.org/0000-0001-6833-3811)
Institutions
- The University of Sydney (AU)
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Khon Kaen University (TH)
- University of California, San Francisco (US)
- Johns Hopkins Medicine (US)
- National Institute of Allergy and Infectious Diseases (US)
- Fundação Oswaldo Cruz (BR)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-25
- DOI
- https://doi.org/10.1038/s41467-026-72421-9
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Frederick National Laboratory for Cancer Research
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases