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IFNγ-independent control of Mycobacterium tuberculosis infection in rhesus macaques

ABSTRACT: Control of Mycobacterium tuberculosis (Mtb) infection requires IFNγ in mice. In humans, IFNγ is critical for resistance to non-tuberculous mycobacteria (NTM), but its role in classic pulmonary tuberculosis is less clear. Here we block IFNγR1 signaling in rhesus macaques at different times post-infection. Short-term IFNγ blockade after tuberculoma formation rapidly reduced 18FDG-PET/CT scores of lung inflammation and changed macrophage gene expression. It also increased IFNβ, pDCs, plasma cells, killers and IFN-driven gene expression in neutrophils. Blockade started on the day of infection altered T and B cell responses and reduced cytokine levels in granulomas. Surprisingly, IFNγ blockade did not affect bacterial loads. We also find that patients with anti-IFNγ neutralizing autoantibodies develop extrapulmonary NTM disease, not pulmonary tuberculosis, despite immunological evidence of Mtb exposure. Thus, IFNγ has broad immunomodulatory effects during tuberculosis, especially on antiviral-like responses, but control of pulmonary Mtb infection does not require generating high levels of IFNγ.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE303792 | GEO | 2026/02/25

REPOSITORIES: GEO

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IFNγ-independent control of Mycobacterium tuberculosis infection in rhesus macaques

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