title: Intracellular survival and persistence of Chlamydia muridarum is determined by macrophage polarization.
abstract: Macrophages can display a number of distinct phenotypes, known collectively as polarized macrophages. The best defined of these phenotypes are the classically-activated, interferon gamma (IFNγ)/LPS induced (M1) and alternatively-activated, IL-4 induced (M2) macrophages. The goal of this study is to characterize macrophage-Chlamydia interactions in the context of macrophage polarization. Here we use Chlamydia muridarum and murine bone-marrow derived macrophages to show Chlamydia does not induce M2 polarization in macrophages as a survival strategy. Unexpectedly, the infection of macrophages was silent with no upregulation of M1 macrophage-associated genes. We further demonstrate that macrophages polarized prior to infection have a differential capacity to control Chlamydia. M1 macrophages harbor up to 40-fold lower inclusion forming units (IFU) than non-polarized or M2 polarized macrophages. Gene expression analysis showed an increase in 16sRNA in M2 macrophages with no change in M1 macrophages. Suppressed Chlamydia growth in M1 macrophages correlated with the induction of a bacterial gene expression profile typical of persistence as evident by increased Euo expression and decreased Omp1 and Tal expression. Observations of permissive Chlamydia growth in non-polarized and M2 macrophages and persistence in M1 macrophages were supported through electron microscopy. This work supports the importance of IFNγ in the innate immune response to Chlamydia. However, demonstration that the M1 macrophages, despite an antimicrobial signature, fail to eliminate intracellular Chlamydia supports the notion that host-pathogen co-evolution has yielded a pathogen that can evade cellular defenses against this pathogen, and persist for prolonged periods of time in the host.
authors: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors: Eric
authors: E
authors: Gracey
authors: Aifeng
authors: A
authors: Lin
authors: Ali
authors: A
authors: Akram
authors: Basil
authors: B
authors: Chiu
authors: Robert D
authors: RD
authors: Inman
mesh_terms: D000818:Animals; D016764:Cell Polarity; D023502:Chlamydia muridarum / Q000254:growth & development / Q000502:physiology*; D042541:Intracellular Space / Q000382:microbiology*; D008264:Macrophages / Q000166:cytology* / Q000382:microbiology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability
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