Lack of B7-1 and B7-2 costimulatory molecules modulates the severity of group B Streptococcus-induced arthritis.
Group B streptococci have long been known as a leading cause of life-threatening infection in neonates, young infants and pregnant women, and recently have been recognized as an ever-growing cause of serious invasive infections in nonpregnant adults. B7-1 and B7-2 are two molecules with immunoregulatory functions implicated in the differentiation of T cells. The present study examined the role of B7-1 and B7-2 during group B streptococci-induced sepsis and arthritis. B7-1- or B7-2-deficient mice were infected with 1x10(7) streptococci, and mortality, appearance of arthritis, growth of microorganisms in the organs and cytokine profile were assessed. Lack of B7-1 was associated with amelioration of arthritis, while worsening of articular lesions was found in B7-2 deficient mice, in comparison to controls. Amelioration of arthritis in B7-1 deficient mice was accompanied by a lower local production of IL-1 beta and IL-18, and increase in IL-4 and IL-10 secretion. On the contrary, B7-2 deficient mice showed an higher proinflammatory cytokine production and lower IL-10 secretion than controls. Taken together, our results provide evidence that signaling delivered by B7-1 and B7-2 plays a role in determining the outcome of group B streptococcal induced arthritis, likely due to the different local secretory pattern.
Puliti
Manuela
M
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Bistoni
Francesco
F
Tissi
Luciana
L
D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013292:Streptococcus agalactiae / Q000472:pathogenicity*; D016019:Survival Analysis
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines