title: Role of Hcp, a type 6 secretion system effector, of Aeromonas hydrophila in modulating activation of host immune cells.
abstract: Recently, we reported that the type 6 secretion system (T6SS) of Aeromonas hydrophila SSU plays an important role in bacterial virulence in a mouse model, and immunization of animals with the T6SS effector haemolysin co-regulated protein (Hcp) protected them against lethal infections with wild-type bacteria. Additionally, we showed that the mutant bacteria deleted for the vasH gene within the T6SS gene cluster did not express the hcp gene, while the vasK mutant could express and translocate Hcp, but was unable to secrete it into the extracellular milieu. Both of these A. hydrophila SSU mutants were readily phagocytosed by murine macrophages, pointing to the possible role of the secreted form of Hcp in the evasion of the host innate immunity. By using the ΔvasH mutant of A. hydrophila, our in vitro data showed that the addition of exogenous recombinant Hcp (rHcp) reduced bacterial uptake by macrophages. These results were substantiated by increased bacterial virulence when rHcp was added along with the ΔvasH mutant in a septicaemic mouse model of infection. Analysis of the cytokine profiling in the intraperitoneal lavage as well as activation of host cells after 4&emsp14;h of infection with the ΔvasH mutant supplemented with rHcp indicated that this T6SS effector inhibited production of pro-inflammatory cytokines and induced immunosuppressive cytokines, such as interleukin-10 and transforming growth factor-β, which could circumvent macrophage activation and maturation. This mechanism of innate immune evasion by Hcp possibly inhibited the recruitment of cellular immune components, which allowed bacterial multiplication and dissemination in animals, thereby leading to their mortality.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Suarez
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Sierra
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Kirtley
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chopra
mesh_terms: D016980:Aeromonas hydrophila / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D051379:Mice; D010587:Phagocytosis; D021381:Protein Transport; D014774:Virulence
chemical_list: D001426:Bacterial Proteins
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