Role for the CD28 molecule in the control of Coxiella burnetii infection.
Q fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular bacterium that replicates in macrophages. As cell-mediated immune response to microbial pathogens requires signals mediated by T-cell receptors and costimulatory molecules such as CD28, we wondered if CD28 is involved in protection against C. burnetii infection. CD28-deficient (CD28-/-) mice were inoculated with C. burnetii by intraperitoneal and intravenous routes. With both wild-type and CD28-/- mice, C. burnetii organisms were detected exclusively in spleen and liver. The antibody response against C. burnetii was impaired in CD28-/- animals, but, surprisingly, the lack of CD28 decreased C. burnetii burden in the infected tissues, whatever the manner of inoculation of bacteria. The CD28 deficiency had no effect on either granuloma formation, which reflects cell-mediated immunity against C. burnetii, or the production of gamma interferon and tumor necrosis factor, two cytokines known to be involved in granuloma formation. On the other hand, the production of interleukin-10 (IL-10) by peritoneal macrophages was highly impaired in CD28-/- mice. The results suggest that CD28 initiates a signal that favors C. burnetii replication through the modulation of the IL-10 pathway.
Unité des Rickettsies, Université de la Méditerranée, Faculté de Médecine, 27 Blvd. J. Moulin, 13385 Marseille Cedex 5, France.
Amélie
A
Honstettre
Soraya
S
Meghari
Jacques A
JA
Nunès
Hubert
H
Lepidi
Didier
D
Raoult
Daniel
D
Olive
Jean-Louis
JL
Mege
D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism / Q000502:physiology*; D016997:Coxiella burnetii / Q000502:physiology*; D007263:Infusions, Parenteral; D016753:Interleukin-10 / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C
D018106:CD28 Antigens; D016753:Interleukin-10