title: The chemokine CXCL12 is essential for the clearance of the filaria Litomosoides sigmodontis in resistant mice.
abstract: Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms.
authors.affiliation: UMR 7245 MCAM MNHN CNRS & UMR 7205 OSEB MNHN CNRS, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Bouchery
authors.forename: Gaelle
authors.initials: G
authors.lastname: Dénécé
authors.forename: Tarik
authors.initials: T
authors.lastname: Attout
authors.forename: Katharina
authors.initials: K
authors.lastname: Ehrhardt
authors.forename: Nathaly
authors.initials: N
authors.lastname: Lhermitte-Vallarino
authors.forename: Muriel
authors.initials: M
authors.lastname: Hachet-Haas
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Galzi
authors.forename: Emilie
authors.initials: E
authors.lastname: Brotin
authors.forename: Françoise
authors.initials: F
authors.lastname: Bachelerie
authors.forename: Laurent
authors.initials: L
authors.lastname: Gavotte
authors.forename: Catherine
authors.initials: C
authors.lastname: Moulia
authors.forename: Odile
authors.initials: O
authors.lastname: Bain
authors.forename: Coralie
authors.initials: C
authors.lastname: Martin
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000502:physiology*; D005368:Filariasis / Q000276:immunology*; D005370:Filarioidea; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse