Immunomodulatory and protective Roles of quorum-sensing signaling molecules N-Acyl homoserine lactones during infection of mice with Aeromonas hydrophila

Bijay K. Khajanchi, Michelle L. Kirtley, Sheri M. Brackman, Ashok Chopra

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Aeromonas hydrophila leads to both intestinal and extraintestinal infections in animals and humans, and the underlying mechanisms leading to mortality are largely unknown. By using a septicemic mouse model of infection, we showed that animals challenged with A. hydrophila die because of kidney and liver damage, hypoglycemia, and thrombocytopenia. Pretreatment of animals with quorum-sensing-associated signaling molecules N-acyl homoserine lactones (AHLs), such as butanoyl and hexanoyl homoserine lactones (C4- and C6-HSLs), as well as N-3-oxododecanoyl (3-oxo-C12)-HSL, prevented clinical sequelae, resulting in increased survivability of mice. Since little is known as to how different AHLs modulate the immune response during infection, we treated mice with the above AHLs prior to lethal A. hydrophila infection. When we compared results in such animals to those in controls, the treated animals exhibited a significantly reduced bacterial load in the blood and other mouse organs, as well as various levels of cytokines/chemokines. Importantly, neutrophil numbers were significantly elevated in the blood of C6-HSL-treated mice compared to those in animals given phosphate-buffered saline and then infected with the bacteria. These findings coincided with the fact that neutropenic animals were more susceptible to A. hydrophila infection than normal mice. Our data suggested that neutrophils quickly cleared bacteria by either phagocytosis or possibly another mechanism(s) during infection. In a parallel study, we indeed showed that other predominant immune cells inflicted during A. hydrophila infections, such as murine macrophages, when they were pretreated with AHLs, rapidly phagocytosed bacteria, whereas untreated cells phagocytosed fewer bacteria. This study is the first to report that AHL pretreatment modulates the innate immune response in mice and enhances their survivability during A. hydrophila infection.

Original languageEnglish (US)
Pages (from-to)2646-2657
Number of pages12
JournalInfection and Immunity
Volume79
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Acyl-Butyrolactones
Aeromonas hydrophila
Quorum Sensing
Infection
Bacteria
Phagocytosis
Neutrophils
Cytophagocytosis
Bacterial Load
Chemokines
Hypoglycemia
Innate Immunity
Thrombocytopenia
Macrophages
Phosphates
Cytokines
Kidney

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Immunomodulatory and protective Roles of quorum-sensing signaling molecules N-Acyl homoserine lactones during infection of mice with Aeromonas hydrophila. / Khajanchi, Bijay K.; Kirtley, Michelle L.; Brackman, Sheri M.; Chopra, Ashok.

In: Infection and Immunity, Vol. 79, No. 7, 07.2011, p. 2646-2657.

Research output: Contribution to journalArticle

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