title: Damage/Danger Associated Molecular Patterns (DAMPs) Modulate Chlamydia pecorum and C. trachomatis Serovar E Inclusion Development In Vitro.
abstract: Persistence, more recently termed the chlamydial stress response, is a viable but non-infectious state constituting a divergence from the characteristic chlamydial biphasic developmental cycle. Damage/danger associated molecular patterns (DAMPs) are normal intracellular components or metabolites that, when released from cells, signal cellular damage/lysis. Purine metabolite DAMPs, including extracellular ATP and adenosine, inhibit chlamydial development in a species-specific manner. Viral co-infection has been shown to reversibly abrogate Chlamydia inclusion development, suggesting persistence/chlamydial stress. Because viral infection can cause host cell DAMP release, we hypothesized DAMPs may influence chlamydial development. Therefore, we examined the effect of extracellular ATP, adenosine, and cyclic AMP exposure, at 0 and 14 hours post infection, on C. pecorum and C. trachomatis serovar E development. In the absence of de novo host protein synthesis, exposure to DAMPs immediately post or at 14 hours post infection reduced inclusion size; however, the effect was less robust upon 14 hours post infection exposure. Additionally, upon exposure to DAMPs immediately post infection, bacteria per inclusion and subsequent infectivity were reduced in both Chlamydia species. These effects were reversible, and C. pecorum exhibited more pronounced recovery from DAMP exposure. Aberrant bodies, typical in virus-induced chlamydial persistence, were absent upon DAMP exposure. In the presence of de novo host protein synthesis, exposure to DAMPs immediately post infection reduced inclusion size, but only variably modulated chlamydial infectivity. Because chlamydial infection and other infections may increase local DAMP concentrations, DAMPs may influence Chlamydia infection in vivo, particularly in the context of poly-microbial infections.
authors.affiliation: Department of Pathobiology, Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland.
authors.forename: Cory Ann
authors.initials: CA
authors.lastname: Leonard
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Schoborg
authors.affiliation: Department of Pathobiology, Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Borel
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001081:Apyrase / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D002689:Chlamydia / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D000242:Cyclic AMP / Q000494:pharmacology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans
chemical_list: D001593:Benzyl Compounds; C509055:erythro-(3-nonyl-p-aminobenzyl-adenine); D015124:8-Bromo Cyclic Adenosine Monophosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D001081:Apyrase; D000225:Adenine; D000241:Adenosine