title: Perforin-2 restricts growth of Chlamydia trachomatis in macrophages.
abstract: Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium that preferentially infects epithelial cells. Professional phagocytes provide C. trachomatis only a limited ability to survive and are proficient killers of chlamydiae. We present evidence herein that identifies a novel host defense protein, perforin-2, that plays a significant role in the eradication of C. trachomatis during the infection of macrophages. Knockdown of perforin-2 in macrophages did not alter the invasion of host cells but did result in chlamydial growth that closely mirrored that detected in HeLa cells. C trachomatis L2, serovar B, and serovar D and C. muridarum were all equally susceptible to perforin-2-mediated killing. Interestingly, induction of perforin-2 expression in epithelial cells is blocked during productive chlamydial growth, thereby protecting chlamydiae from bactericidal attack. Ectopic expression of perforin-2 in HeLa cells, however, does result in killing. Overall, our data implicate a new innate resistance protein in the control of chlamydial infection and may help explain why the macrophage environment is hostile to chlamydial growth.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA. Kfields@med.miami.edu
authors.forename: K A
authors.initials: KA
authors.lastname: Fields
authors.forename: R
authors.initials: R
authors.lastname: McCormack
authors.forename: L R
authors.initials: LR
authors.lastname: de Armas
authors.forename: E R
authors.initials: ER
authors.lastname: Podack
mesh_terms: D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000276:immunology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D052899:Pore Forming Cytotoxic Proteins; C510469:perforin 2