Role for the CD28 Molecule in the Control ofCoxiella burnetiiInfection

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Abstract
Q fever is an infectious disease caused byCoxiella 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 againstC. burnetiiinfection. CD28-deficient (CD28−/−) mice were inoculated withC. burnetiiby intraperitoneal and intravenous routes. With both wild-type and CD28−/−mice,C. burnetiiorganisms were detected exclusively in spleen and liver. The antibody response againstC. burnetiiwas impaired in CD28−/−animals, but, surprisingly, the lack of CD28 decreasedC. burnetiiburden 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 againstC. 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 favorsC. burnetiireplication through the modulation of the IL-10 pathway.