CD46 Contributes to the severity of group A streptococcal infection.
Streptococcus pyogenes (group A Streptococcus) is a human pathogen that causes a wide variety of diseases ranging from uncomplicated superficial infections to severe infections such as streptococcal toxic shock syndrome and necrotizing fasciitis. These bacteria interact with several host cell receptors, one of which is the cell surface complement regulator CD46. In this study, we demonstrate that infection of epithelial cells with S. pyogenes leads to the shedding of CD46 at the same time as the bacteria induce apoptosis and cell death. Soluble CD46 attached to the streptococcal surface, suggesting that bacteria might bind available extracellular CD46 as a strategy to survive and avoid host defenses. The protective role of human CD46 was demonstrated in ex vivo whole-blood assays showing that the growth of S. pyogenes was enhanced in blood from mice expressing human CD46. Finally, in vivo experimental infection showed that bacteremia levels, arthritis frequency, and mortality were higher in CD46 transgenic mice than in nontransgenic mice. Taken together, these results argue that bacterial exploitation of human CD46 enhances bacterial survival and represents a novel pathogenic mechanism that contributes to the severity of group A streptococcal disease.
Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
Lena
L
Lövkvist
Hong
H
Sjölinder
Rahma
R
Wehelie
Helena
H
Aro
Anna
A
Norrby-Teglund
Laura
L
Plant
Ann-Beth
AB
Jonsson
D000818:Animals; D017209:Apoptosis; D001170:Arthritis, Infectious / Q000382:microbiology; D016470:Bacteremia; D001769:Blood / Q000382:microbiology; D016923:Cell Death; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D051916:Membrane Cofactor Protein / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D012720:Severity of Illness Index; D013290:Streptococcal Infections / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D013297:Streptococcus pyogenes / Q000254:growth & development / Q000276:immunology*; D016019:Survival Analysis; D014774:Virulence
C497857:CD46 protein, human; D051916:Membrane Cofactor Protein