{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:26:18Z","timestamp":1790839578783,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T00:00:00Z","timestamp":1157068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycobacterium tuberculosis (strain H37Rv) and bacillus Calmette-Gue\u0301rin (BCG) vaccine inhibit phagosome maturation in macrophages and their effect on processing, and presentation of a secreted Ag85 complex B protein, Ag85B, by mouse macrophages was analyzed. Macrophages were infected with GFP-expressing mycobacterial strains and analyzed for in situ localization of vacuolar proton ATPase (v-ATPase) and cathepsin D (Cat D) using Western blot analysis and immunofluorescence. H37Rv and BCG phagosomes excluded the v-ATPase and maintained neutral pH while the attenuated H37Ra strain acquired v-ATPase and acidified. Mycobacterial phagosomes acquired Cat D, although strains BCG and H37Rv phagosomes contained the inactive 46-kDa form, whereas H37Ra phagosomes had the active 30-kDa form. Infected macrophages were overlaid with a T cell hybridoma specific for an Ag85B epitope complexed with MHC class II. Coincident with active Cat D, H37Ra-infected macrophages presented the epitope to T cells inducing IL-2, whereas H37Rv- and BCG-infected macrophages were less efficient in IL-2 induction. Bafilomycin inhibited the induction of macrophage-induced IL-2 from T cells indicating that v-ATPase was essential for macrophage processing of Ag85B. Furthermore, the small interfering RNA interference of Cat D synthesis resulted in a marked decrease in the levels of macrophage-induced IL-2. Thus, a v-ATPase-dependent phagosomal activation of Cat D was required for the generation of an Ag85B epitope by macrophages. Reduced processing of Ag85B by H37Rv- and BCG-infected macrophages suggests that phagosome maturation arrest interferes with the efficient processing of Ags in macrophages. Because Ag85B is immunodominant, this state may lead to a decreased ability of the wild-type as well as the BCG vaccine to induce protective immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.177.5.3250","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:38:50Z","timestamp":1397849930000},"page":"3250-3259","source":"Crossref","is-referenced-by-count":69,"title":["Processing and Presentation of a Mycobacterial Antigen 85B Epitope by Murine Macrophages Is Dependent on the Phagosomal Acquisition of Vacuolar Proton ATPase and In Situ Activation of Cathepsin D"],"prefix":"10.1093","volume":"177","author":[{"given":"Christopher R","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A","family":"Moulton","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Y","family":"Armitige","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil","family":"Bidani","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Snuggs","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Texas Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramanian","family":"Dhandayuthapani","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Health Science Center , San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinnaswamy","family":"Jagannath","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,9,1]]},"reference":[{"key":"2026020209035929400_R1","first-page":"S58","volume-title":"Indian J. 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