All Phenotypes Mir27a<em1Bge> MGI Mouse

abnormal macrophage physiology ( J:267961 )

• primary peritoneal macrophages isolated from mice infected with Mycobacterium tuberculosis (Mtb) strain H37Rv for 24 hrs exhibit no change in cell cytotoxicity but show reduced intracellular bacterial survival relative to Mtb-infected wild-type macrophages

• pretreatment with the Ca²⁺ inhibitor bepridil (BPD) eliminates the reduction of intracellular bacterial survival seen in Mtb-infected macrophages

• however, peritoneal macrophages pretreated with either AR-12 (an autophagy inducer targeting PDK-1) or Bafilomycin A1 (a vacuolar-ATPase inhibitor that suppresses the autophagic flux at the autophagosome-lysosome fusion stage) and then infected with Mtb show no changes in intracellular survival of Mtb relative to similarly treated wild-type macrophages

decreased susceptibility to bacterial infection ( J:267961 )

• at 28 days post-infection with Mycobacterium tuberculosis (Mtb) strain H37Rv, mice exhibit a lower granuloma score, less infiltration of neutrophils and lymphocytes, and lower bacterial burden in lung tissue than Mtb-infected wild-type controls

• however, mice infected with Mtb H37Rv for 14 days and then treated with an Mir27a antagomir for another 14 days show no differences in granuloma scores, pathological impairment, or bacterial burden in their lung relative to similarly treated wild-type controls

enhanced autophagy ( J:267961 )

• primary peritoneal macrophages infected with Mtb show a marked increase in the production of LC3-II and the autophagosome-autophagolysosome conversion

• peritoneal macrophages pretreated with chloroquine (CQ) and then infected with Mtb show increased autophagosome formation and LC3-II amount in the presence of CQ

• pretreatment with the Ca²⁺ inhibitor bepridil (BPD) eliminates the enhanced formation of LC3 puncta seen in Mtb-infected macrophages

increased calcium level ( J:267961 )

• macrophages infected with Mtb for 1 min show enhanced Ca²⁺ influx relative to wild-type macrophages

abnormal protein level ( J:267961 )

• peritoneal macrophages treated with peptidoglycan (PGN, a TLR2 ligand) show significantly increased mRNA levels of Cacna2d3 (calcium channel, voltage-dependent, alpha2/delta subunit 3; an ER-located Ca²⁺ transporter)

• macrophages infected with Mtb and lungs of Mtb-infected mice show markedly increased Cacna2d3 mRNA and protein levels