Footpad swelling and tissue pathology are reduced upon vaccination with BCG MU-Ag85A.

<p>C57BL/6 mice were left unprimed or were subcutaneously primed with 10⁷ BCG transformed with empty vector (BCG pHA), or BCG MU-Ag85A. At 8 weeks post-prime, mice were intravenously boosted with 10⁷<i>Msmeg</i> expressing MU-Ag85A. Two weeks following the boost, mice were challenged with 10⁵ MU1615 intradermally via the left hind leg footpad. Shown are representative images of infected footpads at 3, 6, and 15 weeks post-challenge. Mice were euthanized if vertical swelling surpassed 4.5 mm, as was the case for unprimed mice before week 15. B. Representative H&E stained tissue sections from 12 week MU-infected mouse footpads are shown. Paws of unprimed mice (UN) consistently showed ulceration (loss of epidermis) with abundant necrosis (N) and infiltrates of inflammatory cells (*). Edema (E) remained prominent in BCG pHA-primed (B) mice but was rarely associated with BCG MU-Ag85A-primed (BA) mouse footpads. Scale bar, 100 μm. C. Representative Ziehl-Neelson (ZN, top row) and H&E (bottom row)-stained tissue sections from 12 week MU-infected mouse footpads are shown. Granulomatous lesions (G) and large masses of acid fast bacilli (AFB,*) are apparent in unprimed footpads (UN), while groups of extracellular AFB were detected in BCG-primed mice (B). AFB generally presented as single scattered extracellular bacteria in footpad tissues from BCG MU-Ag85A-primed mice (BA) and could not be detected in the footpad sections available for ZN staining. Scale bars indicate 100 μm.