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. Author manuscript; available in PMC: 2019 May 12.
Published in final edited form as: Nat Microbiol. 2018 Nov 12;4(1):62–70. doi: 10.1038/s41564-018-0280-x

Fig. 4. MRC-1 mediates pneumolysin-induced suppression of early inflammatory responses in vivo.

Fig. 4

(a) Primary alveolar macrophages were isolated from C57/BL6J mice infected with T4 or T4∆ply at 6 hrs pi. Immunofluorescence staining showed that PLY proficient pneumococci (T4) co-localize with MRC-1 unlike T4∆ply that co-localizes with the lysosome marker (lysotracker). Scale bars, 5μm. Images are representative of data from 5 mice/group. (b) TNF-α levels (N=12) and (c) bacterial count (CFU/mL) (N=13) in BALF from mice infected with either T4 or T4∆ply at 6 hrs pi. Data are mean ± S.E.M of three independent experiments. **P< 0.01 by Mann-Whitney (two-tailed) test. (d) Levels of TNF-α (N=8), and (e) bacterial count (CFU/mL) (N=9) in BALF of mice pretreated with anti-MRC-1 (0.1 mg/mL) or isotype antibody and infected with strain T4 for 6 hrs. Data are mean ± S.E.M of three independent experiments. **P< 0.01 by Mann-Whitney (two-tailed) test. (f) Bacterial count (CFU) per mg nasopharyngeal homogenates of wild type or MRC-1-/- mice infected with strain D39 over a 14 day carriage experiment. N=6 mice per data point per strain, data represent mean ±S.E.M. and analyzed by two-way ANOVA with Tukey’s post-test. (g) Model suggested for PLY-mediated immunomodulation. PLY-proficient pneumococci induce internalization into alveolar macrophages and DCs via interaction with MRC-1. PLY-expressing pneumococci co-localize with MRC-1 in non-lysosomal compartments and block inflammatory cytokine secretion by upregulating SOCS1, thereby promoting regulatory T cell responses and bacterial survival in the airways. **P< 0.01, *** P< 0.001.