Perforin-2 Restricts Growth of Chlamydia trachomatis in Macrophages

Abstract

ABSTRACTChlamydia trachomatisis a Gram-negative obligate intracellular bacterium that preferentially infects epithelial cells. Professional phagocytes provideC. trachomatisonly 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 ofC. trachomatisduring 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 trachomatisL2, serovar B, and serovar D andC. muridarumwere 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.