title: Experimental meningococcal sepsis in congenic transgenic mice expressing human transferrin.
abstract: Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin. We studied experimental meningococcal sepsis in congenic transgenic BALB/c mice expressing human transferrin by transcriptional profiling using microarray analysis of blood and brain samples. Genes encoding acute phase proteins, chemokines and cytokines constituted the largest strongly regulated groups. Dynamic bioluminescence imaging further showed high blood bacterial loads that were further enhanced after a primary viral infection by influenza A virus. Moreover, IL-1 receptor-associated kinase-3 (IRAK-3) was induced in infected mice. IRAK-3 is a negative regulator of Toll-dependant signaling and its induction may impair innate immunity and hence result in an immunocompromised state allowing bacterial survival and systemic spread during sepsis. This new approach should enable detailed analysis of the pathophysiology of meningococcal sepsis and its relationships with flu infection.
authors.affiliation: Unité des Infections Bactérienne Invasives, Institut Pasteur, Paris, France.
authors.forename: Marek
authors.initials: M
authors.lastname: Szatanik
authors.forename: Eva
authors.initials: E
authors.lastname: Hong
authors.forename: Corinne
authors.initials: C
authors.lastname: Ruckly
authors.forename: Morgan
authors.initials: M
authors.lastname: Ledroit
authors.forename: Dario
authors.initials: D
authors.lastname: Giorgini
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jopek
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nicola
authors.forename: Ala-Eddine
authors.initials: AE
authors.lastname: Deghmane
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000097:blood; D005786:Gene Expression Regulation; D006801:Humans; D009980:Influenza A virus / Q000502:physiology; D019570:Inhalation Exposure; D007274:Injections, Intraperitoneal; D008589:Meningococcal Infections / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000821:virology; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009345:Neisseria meningitidis / Q000254:growth & development / Q000502:physiology; D018805:Sepsis / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000821:virology; D016019:Survival Analysis; D014168:Transferrin / Q000378:metabolism*
chemical_list: D016207:Cytokines; D014168:Transferrin