Modulation of endocytosis in nuclear factor IL-6(-/-) macrophages is responsible for a high susceptibility to intracellular bacterial infection.
Activated macrophages kill bacteria, a function known to depend on the expression of NF-IL-6. Here, it is demonstrated that the attenuated Brucella abortus vaccine strain 19 replicates much better in NF-IL-6-/- than in NF-IL-6(+/+) and NF-IL-6(+/+)-activated murine macrophages and at levels comparable to those observed in normal macrophages infected with the pathogenic strain 2308. The role of NF-IL-6 in the inhibition of intracellular bacterial replication is related to its control of endocytosis and membrane fusion between endosomes and Brucella-containing phagosomes. Addition of the granulocyte-CSF (G-CSF), whose induction is impaired in NF-IL-6(-/-) macrophages, restores both endocytosis and the morphology of endosomes, together with bactericidal activity. Regulation of membrane traffic in endocytosis by G-CSF whose expression is controlled by NF-IL-6 may explain how a host cell can control intracellular bacterial replication.
Pizarro-Cerdá
J
J
Centre d'Immunologie de Marseille-Luminy, France.
Desjardins
M
M
Moreno
E
E
Akira
S
S
Gorvel
J P
JP
D000818:Animals; D002003:Brucella abortus / Q000254:growth & development / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology*; D011992:Endosomes / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics*; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics; D010588:Phagosomes / Q000235:genetics / Q000473:pathology
D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor