title: Salmonella administration induces a reduction of wheel-running activity via a TLR5-, but not a TLR4, dependent pathway in mice.
abstract: In general, systemic bacterial infections induce sickness behavior. In mice, lipopolysaccharide (LPS), a component of gram-negative bacteria, strongly reduces physical activity via toll-like receptor (TLR) 4. However, gram-negative bacteria, such as Salmonella, also express flagella containing flagellin (FG) which binds to TLR5 and induces pro-inflammatory cytokine production. It is unclear whether FG induces sickness behavior. To determine whether Salmonella administration regulates the reduction of voluntary physical activity in mice, male C3H/HeN (wild type) and C3H/HeJ (tlr4 gene mutated) mice were administered living Salmonella (live) and examined for wheel-running activity. The production of TNF-alpha in RAW 264 cells was measured by the ELISA assay under both live and heat-killed (HK) Salmonella conditions in vitro. Wheel-running activity in both C3H/HeJ and C3H/HeN mice after i.p. injection of live Salmonella (1 x 10(6) CFU/kg) was significantly lower than that in vehicle groups (p < 0.01, respectively), although wheel-running activity in C3H/HeJ mice was not reduced after i.p. injection of HK Salmonella (1 x 10(6) CFU/kg). Furthermore, TNF-alpha production from RAW 264 cells with HK Salmonella treatment at the early phase was higher than that with live Salmonella treatment. Interestingly, gentamicin-treated (GMT) Salmonella, (which have bacterial flagella removed), did not induce reduction of wheel-running activity, although injection of the flagella-rich supernatant of GMT Salmonella significantly reduced it (p < 0.01). Indeed, FG treatment also induced reduction of wheel-running activity in mice (p < 0.01). Our findings suggest that the Salmonella-induced reduction of voluntary physical activity might be regulated by FG via TLR5, but not LPS via TLR4 in mice.
authors.affiliation: Microbiology, Department of Infectious Disease, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shiva
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawanishi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kato
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Woods
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yano
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D005408:Flagellin / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology; D006358:Hot Temperature; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D012481:Salmonella Infections, Animal / Q000276:immunology*; D019779:Salmonella enterica / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005839:Gentamicins; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin