Extended Data Fig. 5: A. muciniphila-mediated effects of reduced TB pathology and bacillus burdens were impaired in the absence of TNF-α signaling.

(a) Experimental diagram for determining whether the effect of A. muciniphila depends on TNF-α signaling during M. tuberculosis infection. Antibiotics pre-treated mice were gavaged with A. muciniphila (2 × 108 CFU) or saline for 3 times per week followed by aerosol M. tuberculosis infection. Mice were injected with 500 μg anti-TNF-α MAb or IgG antibody control at the third day after M. tuberculosis infection and injections were performed every third day for a total of six injections. (b) Gross pathology shows the hemorrhage and necrosis in lungs of M. tuberculosis-infected mice at 5 weeks post infection. Red circles mark the severe, unresolved hemorrhage, massive disruption or caseous necrosis on the lungs of M. tuberculosis-infected mice. (c-d) Hematoxylin and eosin (H&E) staining of four representative lungs (c) and the histological scores (d) of M. tuberculosis-infected mice at 5 weeks post infection. Scale bars, 500 μm (top: original magnification), 200 μm (middle: 2.5×) and 50 μm (bottom: 10×). The red-boxed areas at the top are enlarged below. Yellow arrowheads mark lesions and infiltration of inflammatory cells. (e) Quantification analysis of M. tuberculosis CFU in the lung homogenates of M. tuberculosis-infected mice at 5 weeks post infection. N = 6 mice per group. Data are representative at least two biological replicates.Data are presented as mean + /- SD. Pvalues were calculated by Student’s two-tailed unpaired t-test [(d) and (e)].