Resilience to bacterial infection: difference between species could be due to proteins in serum.
Vertebrates vary in resistance and resilience to infectious diseases, and the mechanisms that regulate the trade-off between these often opposing protective processes are not well understood. Variability in the sensitivity of species to the induction of damaging inflammation in response to equivalent pathogen loads (resilience) complicates the use of animal models that reflect human disease. We found that induction of proinflammatory cytokines from macrophages in response to inflammatory stimuli in vitro is regulated by proteins in the sera of species in inverse proportion to their in vivo resilience to lethal doses of bacterial lipopolysaccharide over a range of 10,000-fold. This finding suggests that proteins in serum rather than intrinsic cellular differences may play a role in regulating variations in resilience to microbe-associated molecular patterns between species. The involvement of circulating proteins as key molecules raises hope that the process might be manipulated to create better animal models and potentially new drug targets.
Warren
H Shaw
HS
Infectious Disease Unit, Institut Pasteur, Paris, France. swarren1@partners.org
Fitting
Catherine
C
Hoff
Eva
E
Adib-Conquy
Minou
M
Beasley-Topliffe
Laura
L
Tesini
Brenda
B
Liang
Xueya
X
Valentine
Catherine
C
Hellman
Judith
J
Hayden
Douglas
D
Cavaillon
Jean-Marc
JM
D000818:Animals; D016470:Bacteremia / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002298:Cardenolides / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D029968:Escherichia coli Proteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008074:Lipoproteins / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010457:Peptidoglycan / Q000276:immunology*; D012503:Saponins / Q000276:immunology*; D013045:Species Specificity
D001425:Bacterial Outer Membrane Proteins; D002298:Cardenolides; D029968:Escherichia coli Proteins; C031163:ExcC protein, E coli; D008074:Lipoproteins; D010457:Peptidoglycan; D012503:Saponins; C034504:digoxin-like factors